Obesity

Adolescents are an increasingly diverse population reflecting changes in the racial, ethnic, and geopolitical milieus of the United States. The World Health Organization classifies adolescence as ages 10 to 19 years.¹ However, given the complexity of adolescent development physically, behaviorally, emotionally, and socially, others propose that adolescence may extend to age 24.²

Recognizing the specific challenges adolescents face is key to providing comprehensive longitudinal health care. Moreover, creating an environment of trust helps to ensure open 2-way communication that can facilitate anticipatory guidance.

Our review focuses on common adolescent issues, including injury from vehicles and firearms, tobacco and substance misuse, obesity, behavioral health, sexual health, and social media use. We discuss current trends and recommend strategies to maximize health and wellness.

Start by framing the visit

Confidentiality

Laws governing confidentiality in adolescent health care vary by state. Be aware of the laws pertaining to your practice setting. In addition, health care facilities may have their own policies regarding consent and confidentiality in adolescent care. Discuss confidentiality with both an adolescent and the parent/guardian at the initial visit. And, to help avoid potential misunderstandings, let them know in advance what will (and will not) be divulged.

The American Academy of Pediatrics has developed a useful tip sheet regarding confidentiality laws (www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/healthy-foster-care-america/Documents/Confidentiality_Laws.pdf). Examples of required (conditional) disclosure include abuse and suicidal or homicidal ideations. Patients should understand that sexually transmitted infections (STIs) are reportable to public health authorities and that potentially injurious behaviors to self or others (eg, excessive drinking prior to driving) may also warrant disclosure(TABLE 1³).

Privacy and general visit structure

Create a safe atmosphere where adolescents can discuss personal issues without fear of repercussion or judgment. While parents may prefer to be present during the visit, allowing for time to visit independently with an adolescent offers the opportunity to reinforce issues of privacy and confidentiality. Also discuss your office policies regarding electronic communication, phone communication, and relaying test results.

A useful paradigm for organizing a visit for routine adolescent care is to use an expanded version of the HEADSS mnemonic (TABLE 2^4,5), which includes questions about an adolescent’s Home, Education, Activities, Drug and alcohol use, Sexual behavior, Suicidality and depression, and other topics. Other validated screening tools include RAAPS (Rapid Adolescent Prevention Screening)⁶ (www.possibilitiesforchange.com/raaps/); the Guidelines for Adolescent Preventive Services⁷; and the Bright Futures recommendations for preventive care from the American Academy of Pediatrics.⁸ Below, we consider important topics addressed with the HEADSS approach.

Continue to: Injury from vehicles and firearms

Motor vehicle accidents and firearm wounds are the 2 leading causes of adolescent injury. In 2016, of the more than 20,000 deaths in children and adolescents (ages 1-19 years), 20% were due to motor vehicle accidents (4074) and 15% were a result of firearm-­related injuries (3143). Among firearm-­related deaths, 60% were homicides, 35% were suicides, and 4% were due to accidental discharge.⁹ The rate of firearm-related deaths among American teens is 36 times greater than that of any other developed nation.⁹ Currently, 1 of every 3 US households with children younger than 18 has a firearm. Data suggest that in 43% of these households, the firearm is loaded and kept in an unlocked location.¹⁰

To aid anticipatory guidance, ask adolescents about firearm and seat belt use, drinking and driving, and suicidal thoughts (TABLE 2^4,5). Advise them to always wear seat belts whether driving or riding as a passenger. They should never drink and drive (or get in a car with someone who has been drinking). Advise parents that if firearms are present in the household, they should be kept in a secure, locked location. Weapons should be separated from ammunition and safety mechanisms should be engaged on all devices.

Tobacco and substance misuse

Tobacco use, the leading preventable cause of death in the United States,¹¹ is responsible for more deaths than alcohol, motor vehicle accidents, suicides, homicides, and HIV disease combined.¹² Most tobacco-associated mortality occurs in individuals who began smoking before the age of 18.¹² Individuals who start smoking early are also more likely to continue smoking through adulthood.

Encouragingly, tobacco use has declined significantly among adolescents over the past several decades. Roughly 1 in 25 high school seniors reports daily tobacco use.¹³ Adolescent smoking behaviors are also changing dramatically with the increasing popularity of electronic cigarettes (“vaping”). Currently, more adolescents vape than smoke cigarettes.¹³ Vaping has additional health risks including toxic lung injury.

Multiple resources can help combat tobacco and nicotine use in adolescents. The US Preventive Services Task Force recommends that primary care clinicians intervene through education or brief counselling to prevent initiation of tobacco use in school-aged children and adolescents.¹⁴ Ask teens about tobacco and electronic cigarette use and encourage them to quit when use is acknowledged. Other helpful office-based tools are the “Quit Line” 800-QUIT-NOW and texting “Quit” to 47848. Smokefree teen (https://teen.smokefree.gov/) is a website that reviews the risks of tobacco and nicotine use and provides age-appropriate cessation tools and tips (including a smartphone app and a live-chat feature). Other useful information is available in a report from the Surgeon General on preventing tobacco use among young adults.¹⁵

Continue to: Alcohol use

Alcohol use. Three in 5 high school students report ever having used alcohol.¹³ As with tobacco, adolescent alcohol use has declined over the past decade. However, binge drinking (≥ 5 drinks on 1 occasion for males; ≥ 4 drinks on 1 occasion for females) remains a common high-risk behavior among adolescents (particularly college students). Based on the Monitoring the Future Survey, 1 in 6 high school seniors reported binge drinking in the past 2 weeks.¹³ While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.¹³

While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.

The National Institute on Alcohol Abuse and Alcoholism has a screening and intervention guide specifically for adolescents.¹⁶A 2-question screening tool asking about personal use of alcohol and use of alcohol by friends is followed by a risk assessment with recommendations to advise young patients not to drink and to assist them with appropriate intervention and follow-up (https://pubs.niaaa.nih.gov/publications/Practitioner/YouthGuide/YouthGuidePocket.pdf).

Illicit drug use. Half of adolescents report using an illicit drug by their senior year in high school.¹³ Marijuana is the most commonly used substance, and laws governing its use are rapidly changing across the United States. Marijuana is illegal in 10 states and legal in 10 states (and the District of Columbia). The remaining states have varying policies on the medical use of marijuana and the decriminalization of marijuana. In addition, cannabinoid (CBD) products are increasingly available. Frequent cannabis use in adolescence has an adverse impact on general executive function (compared with adult users) and learning.¹⁷ Marijuana may serve as a gateway drug in the abuse of other substances,¹⁸ and its use should be strongly discouraged in adolescents.

Of note, there has been a sharp rise in the illicit use of prescription drugs, particularly opioids, creating a public health emergency across the United States.¹⁹ In 2015, more than 4000 young people, ages 15 to 24, died from a drug-related overdose (> 50% of these attributable to opioids).²⁰ Adolescents with a history of substance abuse and behavioral illness are at particular risk. Many adolescents who misuse opioids and other prescription drugs obtain them from friends and relatives.²¹

The Substance Abuse and Mental Health Services Administration (SAMHSA) recommends universal screening of adolescents for substance abuse. This screening should be accompanied by a brief intervention to prevent, mitigate, or eliminate substance use, or a referral to appropriate treatment sources. This process of screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care.²²

Continue to: Obesity and physical activity

Obesity and physical activity

The percentage of overweight and obese adolescents in the United States has more than tripled over the past 40 years,²³ and 1 in 5 US adolescents is obese.²³ Obese teens are at higher risk for multiple chronic diseases, including type 2 diabetes, sleep apnea, and heart disease.²⁴ They are also more likely to be bullied and to have poor self-esteem.²⁵ Only 1 in 5 American high school students engages in 60 or more minutes of moderate-to-­vigorous physical activity on 5 or more days per week.²⁶

Regular physical activity is, of course, beneficial for cardiorespiratory fitness, bone health, weight control, and improved indices of behavioral health.²⁶ Adolescents who are physically active consistently demonstrate better school attendance and grades.¹⁷ Higher levels of physical fitness are also associated with improved overall cognitive performance.²⁴

General recommendations. The Department of Health and Human Services recommends that adolescents get at least 60 minutes of mostly moderate physical activity every day.²⁶ Encourage adolescents to engage in vigorous physical activity (heavy breathing, sweating) at least 3 days a week. As part of their physical activity patterns, adolescents should also engage in muscle-­strengthening and bone-strengthening activities on at least 3 days per week.

Behavioral health

As young people develop their sense of personal identity, they also strive for independence. It can be difficult, at times, to differentiate normal adolescent rebellion from true mental illness. An estimated 17% to 19% of adolescents meet criteria for mental illness, and about 7% have a severe psychiatric disorder.²⁷ Only one-third of adolescents with mental illness receive any mental health services.²⁸

Depression. The 1-year incidence of major depression in adolescents is 3% to 4%, and the lifetime prevalence of depressive symptoms is 25% in all high school students.²⁷ Risk factors include ethnic minority status, poor self-esteem, poor health, recent personal crisis, insomnia, and alcohol/­substance abuse. Depression in adolescent girls is correlated with becoming sexually active at a younger age, failure to use contraception, having an STI, and suicide attempts. Depressed boys are more likely to have unprotected intercourse and participate in physical fights.²⁹ Depressed teens have a 2- to 3-fold greater risk for behavioral disorders, anxiety, and attention-deficit/hyperactivity disorder (ADHD).³⁰

Continue to: Suicide

Suicide. Among individuals 15 to 29 years of age, suicide is the second leading cause of death globally, with an annual incidence of 11 to 15 per 100,000.³¹ Suicide attempts are 10 to 20 times more common than completed suicide.³¹ Males are more likely than females to die by suicide,³² and boys with a history of attempted suicide have a 30-fold increased risk of subsequent successful suicide.³¹ Hanging, drug poisoning, and firearms (particularly for males) are the most common means of suicide in adolescents. More than half of adolescents dying by suicide have coexisting depression.³¹

Adolescents prefer that providers address sexual health and are more likely to respond if asked directly about sexual behaviors.

Characteristics associated with suicidal behaviors in adolescents include impulsivity, poor problem-solving skills, and dichotomous thinking.³¹ There may be a genetic component as well. In 1 of 5 teenage suicides, a precipitating life event such as the break-up of a relationship, cyber-bullying, or peer rejection is felt to contribute.³¹

ADHD. The prevalence of ADHD is 7% to 9% in US school-aged children.³³ Boys more commonly exhibit hyperactive behaviors, while girls have more inattention. Hyperactivity often diminishes in teens, but inattention and impulsivity persist. Sequelae of ADHD include high-risk sexual behaviors, motor vehicle accidents, incarceration, and substance abuse.³⁴ Poor self-esteem, suicidal ideation, smoking, and obesity are also increased.³⁴ ADHD often persists into adulthood, with implications for social relationships and job performance.³⁴

Eating disorders. The distribution of eating disorders is now known to increasingly include more minorities and males, the latter representing 5% to 10% of cases.³⁵ Eating disorders show a strong genetic tendency and appear to be accelerated by puberty. The most common eating disorder (diagnosed in 0.8%-14% of teens) is eating disorder not otherwise specified (NOS).³⁵ Anorexia nervosa is diagnosed in 0.5% of adolescent girls, and bulimia nervosa in 1% to 2%—particularly among athletes and performers.³⁵ Unanticipated loss of weight, amenorrhea, excessive concern about weight, and deceleration in height/weight curves are potential indicators of an eating disorder. When identified, eating disorders are best managed by a trusted family physician, acting as a coordinator of a multidisciplinary team.

Sexual health

Girls begin to menstruate at an average age of 12, and it takes about 4 years for them to reach reproductive maturity.³⁶ Puberty has been documented to start at younger ages over the past 30 years, likely due to an increase in average body mass index and a decrease in levels of physical activity.³⁷ Girls with early maturation are often insecure and self-conscious, with higher levels of psychological distress.³⁸ In boys, the average age for spermarche (first ejaculation) is 13.³⁹ Boys who mature early tend to be taller, be more confident, and express a good body image.⁴⁰ Those who have early puberty are more likely to be sexually active or participate in high-risk behaviors.⁴¹

Continue to: Pregnancy and contraception

Over the past several decades, more US teens have been abstaining from sexual intercourse or have been using effective forms of birth control, particularly condoms and long-acting reversible contraceptives (LARCs).⁴² Teenage birth rates in girls ages 15 to 19 have declined significantly since the 1980s.⁴² Despite this, the teenage birth rate in the United States remains higher than in other industrialized nations, and most teen pregnancies are unintended.⁴³ Disparities in teenage birth rates also persist across racial and socioeconomic lines.⁴⁴

Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.

There are numerous interventions to reduce teen pregnancy, including sex education, contraceptive counseling, the use of mobile apps that track a user’s monthly fertility cycle or issue reminders to take oral contraceptives,⁴⁵ and the liberal distribution of contraceptives and condoms. The Contraceptive CHOICE Project shows that providing free (or low-cost) LARCs influences young women to choose these as their preferred contraceptive method.⁴⁶ Other programs specifically empower girls to convince partners to use condoms and to resist unwanted sexual advances or intimate partner violence.

Adolescents prefer to have their health care providers address the topic of sexual health. Teens are more likely to share information with providers if asked directly about sexual behaviors.⁴⁷TABLE 2^4,5 offers tips for anticipatory guidance and potential ways to frame questions with adolescents in this context. State laws vary with regard to the ability of minors to seek contraception, pregnancy testing, or care/screening for STIs without parental consent. Contraceptive counseling combined with effective screening decrease the incidence of STIs and pelvic inflammatory disease for sexually active teens.⁴⁸

Sexually transmitted infections

Young adolescents often have a limited ability to imagine consequences related to specific actions. In general, there is also an increased desire to engage in experimental behaviors as an expression of developing autonomy, which may expose them to STIs. About half of all STIs contracted in the United States occur in individuals 15 to 24 years of age.⁴⁹ Girls are at particular risk for the sequelae of these infections, including cervical dysplasia and infertility. Many teens erroneously believe that sexual activities other than intercourse decrease their risk of contracting an STI.⁵⁰

Human papillomavirus (HPV) infection is the most common STI in adolescence.⁵¹ In most cases, HPV is transient and asymptomatic. Oncogenic strains may cause cervical cancer or cancers of the anogenital or oropharyngeal systems. Due to viral latency, it is not recommended to perform HPV typing in men or in women younger than 30 years of age; however, Pap tests are recommended every 3 years for women ages 21 to 29. Primary care providers are pivotal in the public health struggle to prevent HPV infection.

Continue to: Universal immunization of all children...

Universal immunization of all children older than 11 years of age against HPV is strongly advised as part of routine well-child care. Emphasize the proven role of HPV vaccination in preventing cervical⁵² and oropharyngeal⁵³ cancers. And be prepared to address concerns raised by parents in the context of vaccine safety and the initiation of sexual behaviors (www.cdc.gov/hpv/hcp/answering-questions.html).

Chlamydia is the second most common STI in the United States, usually occurring in individuals younger than 24.⁵⁴ The CDC estimates that more than 3 million new chlamydial infections occur yearly. These infections are often asymptomatic, particularly in females, but may cause urethritis, cervicitis, epididymitis, proctitis, or pelvic inflammatory disease. Indolent chlamydial infection is the leading cause of tubal infertility in women.⁵⁴ Routine annual screening for chlamydia is recommended for all sexually active females ≤ 25 years (and for older women with specific risks).⁵⁵ Annual screening is also recommended for men who have sex with men (MSM).⁵⁵

Chlamydial infection may be diagnosed with first-catch urine sampling (men or women), urethral swab (men), endocervical swab (women), or self-collected vaginal swab. Nucleic acid amplification testing is the most sensitive test that is widely available.⁵⁶ First-line treatment includes either azithromycin (1 g orally, single dose) or doxycycline (100 mg orally, twice daily for 7 days).⁵⁶

Gonorrhea. In 2018, there were more than 500,000 annual cases of gonorrhea, with the majority occurring in those between 15 and 24 years of age.⁵⁷ Gonorrhea may increase rates of HIV infection transmission up to 5-fold.⁵⁷ As more adolescents practice oral sex, cases of pharyngeal gonorrhea (and oropharyngeal HPV) have increased. Symptoms of urethritis occur more frequently in men. Screening is recommended for all sexually active women younger than 25.⁵⁶ Importantly, the organism Neisseria gonorrhoeae has developed significant antibiotic resistance over the past decade. The CDC currently recommends dual therapy for the treatment of gonorrhea using 250 mg of intramuscular ceftriaxone and 1 g of oral azithromycin.⁵⁶

Syphilis. Rates of syphilis are increasing among individuals ages 15 to 24.⁵¹ Screening is particularly recommended for MSM and individuals infected with HIV. Benzathine penicillin G, 50,000 U/kg IM, remains the treatment of choice.⁵⁶

Continue to: HIV

HIV. Globally, HIV impacts young people disproportionately. HIV infection also facilitates infection with other STIs. In the United States, the highest burden of HIV infection is borne by young MSM, with prevalence among those 18 to 24 years old varying between 26% to 30% (black) and 3% to 5.5% (non-Hispanic white).⁵¹ The use of emtricitabine/tenofovir disoproxil fumarate for pre-exposure prophylaxis (PrEP) has recently been approved for the prevention of HIV. PrEP reduces risk by up to 92% for MSM and transgender women.⁵⁸

Sexual identity

One in 10 high school students self-identifies as “nonheterosexual,” and 1 in 15 reports same-sex sexual contact.⁵⁹ The term LGBTQ+ includes the communities of lesbian, gay, bisexual, transgender, transsexual, queer, questioning, intersex, and asexual individuals. Developing a safe sense of sexual identity is fundamental to adolescent psychological development, and many adolescents struggle to develop a positive sexual identity. Suicide rates and self-harm behaviors among ­LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.⁶⁰ Rates of mood disorders, substance abuse, and high-risk sexual behaviors are also increased in the LGBTQ+ population.⁶¹

Suicide rates and self-harm behaviors among LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.

The LGBTQ+ community often seeks health care advice and affirmation from primary care providers. Resources to enhance this care are available at www.lgbthealtheducation.org.

Social media

Adolescents today have more media exposure than any prior generation, with smartphone and computer use increasing exponentially. Most (95%) teens have access to a smartphone,⁶² 45% describe themselves as constantly connected to the Internet, and 14% feel that social media is “addictive.”⁶² Most manage their social media portfolio on multiple sites. Patterns of adolescents' online activities show that boys prefer online gaming, while girls tend to spend more time on social networking.⁶²

Whether extensive media use is psychologically beneficial or deleterious has been widely debated. Increased time online correlates with decreased levels of physical activity.⁶³ And sleep disturbances have been associated with excessive screen time and the presence of mobile devices in the bedroom.⁶⁴ The use of social media prior to bedtime also has an adverse impact on academic performance—particularly for girls. This adverse impact on academics persists after correcting for daytime sleepiness, body mass index, and number of hours spent on homework.⁶⁴

Continue to: Due to growing concerns...

Due to growing concerns about the risks of social media in children and adolescents, the American Academy of Pediatrics has developed the Family Media Plan (www.healthychildren.org/English/media/Pages/default.aspx). Some specific questions that providers may ask are outlined in TABLE 3.⁶⁴ The Family Media Plan can provide age-specific guidelines to assist parents or caregivers in answering these questions.

Cyber-bullying. One in 3 adolescents (primarily female) has been a victim of cyber-bullying.⁶⁵ Sadly, 1 in 5 teens has received some form of electronic sexual solicitation.⁶⁶ The likelihood of unsolicited stranger contact correlates with teens’ online habits and the amount of information disclosed. Predictors include female sex, visiting chat rooms, posting photos, and disclosing personal information. Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.⁶⁵ While 63% of cyber-bullying victims feel upset, embarrassed, or stressed by these contacts,⁶⁶ few events are actually reported. To address this, some states have adopted laws adding cyber-bullying to school disciplinary codes.

Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.

Negative health impacts associated with cyber-bullying include anxiety, sadness, and greater difficulty in concentrating on school work.⁶⁵ Victims of bullying are more likely to have school disciplinary actions and depression and to be truant or to carry weapons to school.⁶⁶ Cyber-bullying is uniquely destructive due to its ubiquitous presence. A sense of relative anonymity online may encourage perpetrators to act more cruelly, with less concern for punishment.

Young people are also more likely to share passwords as a sign of friendship. This may result in others assuming their identity online. Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.⁶⁶

CORRESPONDENCE
Mark B. Stephens, MD, Penn State Health Medical Group, 1850 East Park Avenue, State College, PA 16803; mstephens3@pennstatehealth.psu.edu.

Adolescents are an increasingly diverse population reflecting changes in the racial, ethnic, and geopolitical milieus of the United States. The World Health Organization classifies adolescence as ages 10 to 19 years.¹ However, given the complexity of adolescent development physically, behaviorally, emotionally, and socially, others propose that adolescence may extend to age 24.²

Recognizing the specific challenges adolescents face is key to providing comprehensive longitudinal health care. Moreover, creating an environment of trust helps to ensure open 2-way communication that can facilitate anticipatory guidance.

Our review focuses on common adolescent issues, including injury from vehicles and firearms, tobacco and substance misuse, obesity, behavioral health, sexual health, and social media use. We discuss current trends and recommend strategies to maximize health and wellness.

Start by framing the visit

Confidentiality

Laws governing confidentiality in adolescent health care vary by state. Be aware of the laws pertaining to your practice setting. In addition, health care facilities may have their own policies regarding consent and confidentiality in adolescent care. Discuss confidentiality with both an adolescent and the parent/guardian at the initial visit. And, to help avoid potential misunderstandings, let them know in advance what will (and will not) be divulged.

The American Academy of Pediatrics has developed a useful tip sheet regarding confidentiality laws (www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/healthy-foster-care-america/Documents/Confidentiality_Laws.pdf). Examples of required (conditional) disclosure include abuse and suicidal or homicidal ideations. Patients should understand that sexually transmitted infections (STIs) are reportable to public health authorities and that potentially injurious behaviors to self or others (eg, excessive drinking prior to driving) may also warrant disclosure(TABLE 1³).

Privacy and general visit structure

Create a safe atmosphere where adolescents can discuss personal issues without fear of repercussion or judgment. While parents may prefer to be present during the visit, allowing for time to visit independently with an adolescent offers the opportunity to reinforce issues of privacy and confidentiality. Also discuss your office policies regarding electronic communication, phone communication, and relaying test results.

A useful paradigm for organizing a visit for routine adolescent care is to use an expanded version of the HEADSS mnemonic (TABLE 2^4,5), which includes questions about an adolescent’s Home, Education, Activities, Drug and alcohol use, Sexual behavior, Suicidality and depression, and other topics. Other validated screening tools include RAAPS (Rapid Adolescent Prevention Screening)⁶ (www.possibilitiesforchange.com/raaps/); the Guidelines for Adolescent Preventive Services⁷; and the Bright Futures recommendations for preventive care from the American Academy of Pediatrics.⁸ Below, we consider important topics addressed with the HEADSS approach.

Continue to: Injury from vehicles and firearms

Motor vehicle accidents and firearm wounds are the 2 leading causes of adolescent injury. In 2016, of the more than 20,000 deaths in children and adolescents (ages 1-19 years), 20% were due to motor vehicle accidents (4074) and 15% were a result of firearm-­related injuries (3143). Among firearm-­related deaths, 60% were homicides, 35% were suicides, and 4% were due to accidental discharge.⁹ The rate of firearm-related deaths among American teens is 36 times greater than that of any other developed nation.⁹ Currently, 1 of every 3 US households with children younger than 18 has a firearm. Data suggest that in 43% of these households, the firearm is loaded and kept in an unlocked location.¹⁰

To aid anticipatory guidance, ask adolescents about firearm and seat belt use, drinking and driving, and suicidal thoughts (TABLE 2^4,5). Advise them to always wear seat belts whether driving or riding as a passenger. They should never drink and drive (or get in a car with someone who has been drinking). Advise parents that if firearms are present in the household, they should be kept in a secure, locked location. Weapons should be separated from ammunition and safety mechanisms should be engaged on all devices.

Tobacco and substance misuse

Tobacco use, the leading preventable cause of death in the United States,¹¹ is responsible for more deaths than alcohol, motor vehicle accidents, suicides, homicides, and HIV disease combined.¹² Most tobacco-associated mortality occurs in individuals who began smoking before the age of 18.¹² Individuals who start smoking early are also more likely to continue smoking through adulthood.

Encouragingly, tobacco use has declined significantly among adolescents over the past several decades. Roughly 1 in 25 high school seniors reports daily tobacco use.¹³ Adolescent smoking behaviors are also changing dramatically with the increasing popularity of electronic cigarettes (“vaping”). Currently, more adolescents vape than smoke cigarettes.¹³ Vaping has additional health risks including toxic lung injury.

Multiple resources can help combat tobacco and nicotine use in adolescents. The US Preventive Services Task Force recommends that primary care clinicians intervene through education or brief counselling to prevent initiation of tobacco use in school-aged children and adolescents.¹⁴ Ask teens about tobacco and electronic cigarette use and encourage them to quit when use is acknowledged. Other helpful office-based tools are the “Quit Line” 800-QUIT-NOW and texting “Quit” to 47848. Smokefree teen (https://teen.smokefree.gov/) is a website that reviews the risks of tobacco and nicotine use and provides age-appropriate cessation tools and tips (including a smartphone app and a live-chat feature). Other useful information is available in a report from the Surgeon General on preventing tobacco use among young adults.¹⁵

Continue to: Alcohol use

Alcohol use. Three in 5 high school students report ever having used alcohol.¹³ As with tobacco, adolescent alcohol use has declined over the past decade. However, binge drinking (≥ 5 drinks on 1 occasion for males; ≥ 4 drinks on 1 occasion for females) remains a common high-risk behavior among adolescents (particularly college students). Based on the Monitoring the Future Survey, 1 in 6 high school seniors reported binge drinking in the past 2 weeks.¹³ While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.¹³

While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.

The National Institute on Alcohol Abuse and Alcoholism has a screening and intervention guide specifically for adolescents.¹⁶A 2-question screening tool asking about personal use of alcohol and use of alcohol by friends is followed by a risk assessment with recommendations to advise young patients not to drink and to assist them with appropriate intervention and follow-up (https://pubs.niaaa.nih.gov/publications/Practitioner/YouthGuide/YouthGuidePocket.pdf).

Illicit drug use. Half of adolescents report using an illicit drug by their senior year in high school.¹³ Marijuana is the most commonly used substance, and laws governing its use are rapidly changing across the United States. Marijuana is illegal in 10 states and legal in 10 states (and the District of Columbia). The remaining states have varying policies on the medical use of marijuana and the decriminalization of marijuana. In addition, cannabinoid (CBD) products are increasingly available. Frequent cannabis use in adolescence has an adverse impact on general executive function (compared with adult users) and learning.¹⁷ Marijuana may serve as a gateway drug in the abuse of other substances,¹⁸ and its use should be strongly discouraged in adolescents.

Of note, there has been a sharp rise in the illicit use of prescription drugs, particularly opioids, creating a public health emergency across the United States.¹⁹ In 2015, more than 4000 young people, ages 15 to 24, died from a drug-related overdose (> 50% of these attributable to opioids).²⁰ Adolescents with a history of substance abuse and behavioral illness are at particular risk. Many adolescents who misuse opioids and other prescription drugs obtain them from friends and relatives.²¹

The Substance Abuse and Mental Health Services Administration (SAMHSA) recommends universal screening of adolescents for substance abuse. This screening should be accompanied by a brief intervention to prevent, mitigate, or eliminate substance use, or a referral to appropriate treatment sources. This process of screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care.²²

Continue to: Obesity and physical activity

Obesity and physical activity

The percentage of overweight and obese adolescents in the United States has more than tripled over the past 40 years,²³ and 1 in 5 US adolescents is obese.²³ Obese teens are at higher risk for multiple chronic diseases, including type 2 diabetes, sleep apnea, and heart disease.²⁴ They are also more likely to be bullied and to have poor self-esteem.²⁵ Only 1 in 5 American high school students engages in 60 or more minutes of moderate-to-­vigorous physical activity on 5 or more days per week.²⁶

Regular physical activity is, of course, beneficial for cardiorespiratory fitness, bone health, weight control, and improved indices of behavioral health.²⁶ Adolescents who are physically active consistently demonstrate better school attendance and grades.¹⁷ Higher levels of physical fitness are also associated with improved overall cognitive performance.²⁴

General recommendations. The Department of Health and Human Services recommends that adolescents get at least 60 minutes of mostly moderate physical activity every day.²⁶ Encourage adolescents to engage in vigorous physical activity (heavy breathing, sweating) at least 3 days a week. As part of their physical activity patterns, adolescents should also engage in muscle-­strengthening and bone-strengthening activities on at least 3 days per week.

Behavioral health

As young people develop their sense of personal identity, they also strive for independence. It can be difficult, at times, to differentiate normal adolescent rebellion from true mental illness. An estimated 17% to 19% of adolescents meet criteria for mental illness, and about 7% have a severe psychiatric disorder.²⁷ Only one-third of adolescents with mental illness receive any mental health services.²⁸

Depression. The 1-year incidence of major depression in adolescents is 3% to 4%, and the lifetime prevalence of depressive symptoms is 25% in all high school students.²⁷ Risk factors include ethnic minority status, poor self-esteem, poor health, recent personal crisis, insomnia, and alcohol/­substance abuse. Depression in adolescent girls is correlated with becoming sexually active at a younger age, failure to use contraception, having an STI, and suicide attempts. Depressed boys are more likely to have unprotected intercourse and participate in physical fights.²⁹ Depressed teens have a 2- to 3-fold greater risk for behavioral disorders, anxiety, and attention-deficit/hyperactivity disorder (ADHD).³⁰

Continue to: Suicide

Suicide. Among individuals 15 to 29 years of age, suicide is the second leading cause of death globally, with an annual incidence of 11 to 15 per 100,000.³¹ Suicide attempts are 10 to 20 times more common than completed suicide.³¹ Males are more likely than females to die by suicide,³² and boys with a history of attempted suicide have a 30-fold increased risk of subsequent successful suicide.³¹ Hanging, drug poisoning, and firearms (particularly for males) are the most common means of suicide in adolescents. More than half of adolescents dying by suicide have coexisting depression.³¹

Adolescents prefer that providers address sexual health and are more likely to respond if asked directly about sexual behaviors.

Characteristics associated with suicidal behaviors in adolescents include impulsivity, poor problem-solving skills, and dichotomous thinking.³¹ There may be a genetic component as well. In 1 of 5 teenage suicides, a precipitating life event such as the break-up of a relationship, cyber-bullying, or peer rejection is felt to contribute.³¹

ADHD. The prevalence of ADHD is 7% to 9% in US school-aged children.³³ Boys more commonly exhibit hyperactive behaviors, while girls have more inattention. Hyperactivity often diminishes in teens, but inattention and impulsivity persist. Sequelae of ADHD include high-risk sexual behaviors, motor vehicle accidents, incarceration, and substance abuse.³⁴ Poor self-esteem, suicidal ideation, smoking, and obesity are also increased.³⁴ ADHD often persists into adulthood, with implications for social relationships and job performance.³⁴

Eating disorders. The distribution of eating disorders is now known to increasingly include more minorities and males, the latter representing 5% to 10% of cases.³⁵ Eating disorders show a strong genetic tendency and appear to be accelerated by puberty. The most common eating disorder (diagnosed in 0.8%-14% of teens) is eating disorder not otherwise specified (NOS).³⁵ Anorexia nervosa is diagnosed in 0.5% of adolescent girls, and bulimia nervosa in 1% to 2%—particularly among athletes and performers.³⁵ Unanticipated loss of weight, amenorrhea, excessive concern about weight, and deceleration in height/weight curves are potential indicators of an eating disorder. When identified, eating disorders are best managed by a trusted family physician, acting as a coordinator of a multidisciplinary team.

Sexual health

Girls begin to menstruate at an average age of 12, and it takes about 4 years for them to reach reproductive maturity.³⁶ Puberty has been documented to start at younger ages over the past 30 years, likely due to an increase in average body mass index and a decrease in levels of physical activity.³⁷ Girls with early maturation are often insecure and self-conscious, with higher levels of psychological distress.³⁸ In boys, the average age for spermarche (first ejaculation) is 13.³⁹ Boys who mature early tend to be taller, be more confident, and express a good body image.⁴⁰ Those who have early puberty are more likely to be sexually active or participate in high-risk behaviors.⁴¹

Continue to: Pregnancy and contraception

Over the past several decades, more US teens have been abstaining from sexual intercourse or have been using effective forms of birth control, particularly condoms and long-acting reversible contraceptives (LARCs).⁴² Teenage birth rates in girls ages 15 to 19 have declined significantly since the 1980s.⁴² Despite this, the teenage birth rate in the United States remains higher than in other industrialized nations, and most teen pregnancies are unintended.⁴³ Disparities in teenage birth rates also persist across racial and socioeconomic lines.⁴⁴

Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.

There are numerous interventions to reduce teen pregnancy, including sex education, contraceptive counseling, the use of mobile apps that track a user’s monthly fertility cycle or issue reminders to take oral contraceptives,⁴⁵ and the liberal distribution of contraceptives and condoms. The Contraceptive CHOICE Project shows that providing free (or low-cost) LARCs influences young women to choose these as their preferred contraceptive method.⁴⁶ Other programs specifically empower girls to convince partners to use condoms and to resist unwanted sexual advances or intimate partner violence.

Adolescents prefer to have their health care providers address the topic of sexual health. Teens are more likely to share information with providers if asked directly about sexual behaviors.⁴⁷TABLE 2^4,5 offers tips for anticipatory guidance and potential ways to frame questions with adolescents in this context. State laws vary with regard to the ability of minors to seek contraception, pregnancy testing, or care/screening for STIs without parental consent. Contraceptive counseling combined with effective screening decrease the incidence of STIs and pelvic inflammatory disease for sexually active teens.⁴⁸

Sexually transmitted infections

Young adolescents often have a limited ability to imagine consequences related to specific actions. In general, there is also an increased desire to engage in experimental behaviors as an expression of developing autonomy, which may expose them to STIs. About half of all STIs contracted in the United States occur in individuals 15 to 24 years of age.⁴⁹ Girls are at particular risk for the sequelae of these infections, including cervical dysplasia and infertility. Many teens erroneously believe that sexual activities other than intercourse decrease their risk of contracting an STI.⁵⁰

Human papillomavirus (HPV) infection is the most common STI in adolescence.⁵¹ In most cases, HPV is transient and asymptomatic. Oncogenic strains may cause cervical cancer or cancers of the anogenital or oropharyngeal systems. Due to viral latency, it is not recommended to perform HPV typing in men or in women younger than 30 years of age; however, Pap tests are recommended every 3 years for women ages 21 to 29. Primary care providers are pivotal in the public health struggle to prevent HPV infection.

Continue to: Universal immunization of all children...

Universal immunization of all children older than 11 years of age against HPV is strongly advised as part of routine well-child care. Emphasize the proven role of HPV vaccination in preventing cervical⁵² and oropharyngeal⁵³ cancers. And be prepared to address concerns raised by parents in the context of vaccine safety and the initiation of sexual behaviors (www.cdc.gov/hpv/hcp/answering-questions.html).

Chlamydia is the second most common STI in the United States, usually occurring in individuals younger than 24.⁵⁴ The CDC estimates that more than 3 million new chlamydial infections occur yearly. These infections are often asymptomatic, particularly in females, but may cause urethritis, cervicitis, epididymitis, proctitis, or pelvic inflammatory disease. Indolent chlamydial infection is the leading cause of tubal infertility in women.⁵⁴ Routine annual screening for chlamydia is recommended for all sexually active females ≤ 25 years (and for older women with specific risks).⁵⁵ Annual screening is also recommended for men who have sex with men (MSM).⁵⁵

Chlamydial infection may be diagnosed with first-catch urine sampling (men or women), urethral swab (men), endocervical swab (women), or self-collected vaginal swab. Nucleic acid amplification testing is the most sensitive test that is widely available.⁵⁶ First-line treatment includes either azithromycin (1 g orally, single dose) or doxycycline (100 mg orally, twice daily for 7 days).⁵⁶

Gonorrhea. In 2018, there were more than 500,000 annual cases of gonorrhea, with the majority occurring in those between 15 and 24 years of age.⁵⁷ Gonorrhea may increase rates of HIV infection transmission up to 5-fold.⁵⁷ As more adolescents practice oral sex, cases of pharyngeal gonorrhea (and oropharyngeal HPV) have increased. Symptoms of urethritis occur more frequently in men. Screening is recommended for all sexually active women younger than 25.⁵⁶ Importantly, the organism Neisseria gonorrhoeae has developed significant antibiotic resistance over the past decade. The CDC currently recommends dual therapy for the treatment of gonorrhea using 250 mg of intramuscular ceftriaxone and 1 g of oral azithromycin.⁵⁶

Syphilis. Rates of syphilis are increasing among individuals ages 15 to 24.⁵¹ Screening is particularly recommended for MSM and individuals infected with HIV. Benzathine penicillin G, 50,000 U/kg IM, remains the treatment of choice.⁵⁶

Continue to: HIV

HIV. Globally, HIV impacts young people disproportionately. HIV infection also facilitates infection with other STIs. In the United States, the highest burden of HIV infection is borne by young MSM, with prevalence among those 18 to 24 years old varying between 26% to 30% (black) and 3% to 5.5% (non-Hispanic white).⁵¹ The use of emtricitabine/tenofovir disoproxil fumarate for pre-exposure prophylaxis (PrEP) has recently been approved for the prevention of HIV. PrEP reduces risk by up to 92% for MSM and transgender women.⁵⁸

Sexual identity

One in 10 high school students self-identifies as “nonheterosexual,” and 1 in 15 reports same-sex sexual contact.⁵⁹ The term LGBTQ+ includes the communities of lesbian, gay, bisexual, transgender, transsexual, queer, questioning, intersex, and asexual individuals. Developing a safe sense of sexual identity is fundamental to adolescent psychological development, and many adolescents struggle to develop a positive sexual identity. Suicide rates and self-harm behaviors among ­LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.⁶⁰ Rates of mood disorders, substance abuse, and high-risk sexual behaviors are also increased in the LGBTQ+ population.⁶¹

Suicide rates and self-harm behaviors among LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.

The LGBTQ+ community often seeks health care advice and affirmation from primary care providers. Resources to enhance this care are available at www.lgbthealtheducation.org.

Social media

Adolescents today have more media exposure than any prior generation, with smartphone and computer use increasing exponentially. Most (95%) teens have access to a smartphone,⁶² 45% describe themselves as constantly connected to the Internet, and 14% feel that social media is “addictive.”⁶² Most manage their social media portfolio on multiple sites. Patterns of adolescents' online activities show that boys prefer online gaming, while girls tend to spend more time on social networking.⁶²

Whether extensive media use is psychologically beneficial or deleterious has been widely debated. Increased time online correlates with decreased levels of physical activity.⁶³ And sleep disturbances have been associated with excessive screen time and the presence of mobile devices in the bedroom.⁶⁴ The use of social media prior to bedtime also has an adverse impact on academic performance—particularly for girls. This adverse impact on academics persists after correcting for daytime sleepiness, body mass index, and number of hours spent on homework.⁶⁴

Continue to: Due to growing concerns...

Due to growing concerns about the risks of social media in children and adolescents, the American Academy of Pediatrics has developed the Family Media Plan (www.healthychildren.org/English/media/Pages/default.aspx). Some specific questions that providers may ask are outlined in TABLE 3.⁶⁴ The Family Media Plan can provide age-specific guidelines to assist parents or caregivers in answering these questions.

Cyber-bullying. One in 3 adolescents (primarily female) has been a victim of cyber-bullying.⁶⁵ Sadly, 1 in 5 teens has received some form of electronic sexual solicitation.⁶⁶ The likelihood of unsolicited stranger contact correlates with teens’ online habits and the amount of information disclosed. Predictors include female sex, visiting chat rooms, posting photos, and disclosing personal information. Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.⁶⁵ While 63% of cyber-bullying victims feel upset, embarrassed, or stressed by these contacts,⁶⁶ few events are actually reported. To address this, some states have adopted laws adding cyber-bullying to school disciplinary codes.

Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.

Negative health impacts associated with cyber-bullying include anxiety, sadness, and greater difficulty in concentrating on school work.⁶⁵ Victims of bullying are more likely to have school disciplinary actions and depression and to be truant or to carry weapons to school.⁶⁶ Cyber-bullying is uniquely destructive due to its ubiquitous presence. A sense of relative anonymity online may encourage perpetrators to act more cruelly, with less concern for punishment.

Young people are also more likely to share passwords as a sign of friendship. This may result in others assuming their identity online. Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.⁶⁶

CORRESPONDENCE
Mark B. Stephens, MD, Penn State Health Medical Group, 1850 East Park Avenue, State College, PA 16803; mstephens3@pennstatehealth.psu.edu.

Adolescents are an increasingly diverse population reflecting changes in the racial, ethnic, and geopolitical milieus of the United States. The World Health Organization classifies adolescence as ages 10 to 19 years.¹ However, given the complexity of adolescent development physically, behaviorally, emotionally, and socially, others propose that adolescence may extend to age 24.²

Recognizing the specific challenges adolescents face is key to providing comprehensive longitudinal health care. Moreover, creating an environment of trust helps to ensure open 2-way communication that can facilitate anticipatory guidance.

Our review focuses on common adolescent issues, including injury from vehicles and firearms, tobacco and substance misuse, obesity, behavioral health, sexual health, and social media use. We discuss current trends and recommend strategies to maximize health and wellness.

Start by framing the visit

Confidentiality

Laws governing confidentiality in adolescent health care vary by state. Be aware of the laws pertaining to your practice setting. In addition, health care facilities may have their own policies regarding consent and confidentiality in adolescent care. Discuss confidentiality with both an adolescent and the parent/guardian at the initial visit. And, to help avoid potential misunderstandings, let them know in advance what will (and will not) be divulged.

The American Academy of Pediatrics has developed a useful tip sheet regarding confidentiality laws (www.aap.org/en-us/advocacy-and-policy/aap-health-initiatives/healthy-foster-care-america/Documents/Confidentiality_Laws.pdf). Examples of required (conditional) disclosure include abuse and suicidal or homicidal ideations. Patients should understand that sexually transmitted infections (STIs) are reportable to public health authorities and that potentially injurious behaviors to self or others (eg, excessive drinking prior to driving) may also warrant disclosure(TABLE 1³).

Privacy and general visit structure

Create a safe atmosphere where adolescents can discuss personal issues without fear of repercussion or judgment. While parents may prefer to be present during the visit, allowing for time to visit independently with an adolescent offers the opportunity to reinforce issues of privacy and confidentiality. Also discuss your office policies regarding electronic communication, phone communication, and relaying test results.

A useful paradigm for organizing a visit for routine adolescent care is to use an expanded version of the HEADSS mnemonic (TABLE 2^4,5), which includes questions about an adolescent’s Home, Education, Activities, Drug and alcohol use, Sexual behavior, Suicidality and depression, and other topics. Other validated screening tools include RAAPS (Rapid Adolescent Prevention Screening)⁶ (www.possibilitiesforchange.com/raaps/); the Guidelines for Adolescent Preventive Services⁷; and the Bright Futures recommendations for preventive care from the American Academy of Pediatrics.⁸ Below, we consider important topics addressed with the HEADSS approach.

Continue to: Injury from vehicles and firearms

Motor vehicle accidents and firearm wounds are the 2 leading causes of adolescent injury. In 2016, of the more than 20,000 deaths in children and adolescents (ages 1-19 years), 20% were due to motor vehicle accidents (4074) and 15% were a result of firearm-­related injuries (3143). Among firearm-­related deaths, 60% were homicides, 35% were suicides, and 4% were due to accidental discharge.⁹ The rate of firearm-related deaths among American teens is 36 times greater than that of any other developed nation.⁹ Currently, 1 of every 3 US households with children younger than 18 has a firearm. Data suggest that in 43% of these households, the firearm is loaded and kept in an unlocked location.¹⁰

To aid anticipatory guidance, ask adolescents about firearm and seat belt use, drinking and driving, and suicidal thoughts (TABLE 2^4,5). Advise them to always wear seat belts whether driving or riding as a passenger. They should never drink and drive (or get in a car with someone who has been drinking). Advise parents that if firearms are present in the household, they should be kept in a secure, locked location. Weapons should be separated from ammunition and safety mechanisms should be engaged on all devices.

Tobacco and substance misuse

Tobacco use, the leading preventable cause of death in the United States,¹¹ is responsible for more deaths than alcohol, motor vehicle accidents, suicides, homicides, and HIV disease combined.¹² Most tobacco-associated mortality occurs in individuals who began smoking before the age of 18.¹² Individuals who start smoking early are also more likely to continue smoking through adulthood.

Encouragingly, tobacco use has declined significantly among adolescents over the past several decades. Roughly 1 in 25 high school seniors reports daily tobacco use.¹³ Adolescent smoking behaviors are also changing dramatically with the increasing popularity of electronic cigarettes (“vaping”). Currently, more adolescents vape than smoke cigarettes.¹³ Vaping has additional health risks including toxic lung injury.

Multiple resources can help combat tobacco and nicotine use in adolescents. The US Preventive Services Task Force recommends that primary care clinicians intervene through education or brief counselling to prevent initiation of tobacco use in school-aged children and adolescents.¹⁴ Ask teens about tobacco and electronic cigarette use and encourage them to quit when use is acknowledged. Other helpful office-based tools are the “Quit Line” 800-QUIT-NOW and texting “Quit” to 47848. Smokefree teen (https://teen.smokefree.gov/) is a website that reviews the risks of tobacco and nicotine use and provides age-appropriate cessation tools and tips (including a smartphone app and a live-chat feature). Other useful information is available in a report from the Surgeon General on preventing tobacco use among young adults.¹⁵

Continue to: Alcohol use

Alcohol use. Three in 5 high school students report ever having used alcohol.¹³ As with tobacco, adolescent alcohol use has declined over the past decade. However, binge drinking (≥ 5 drinks on 1 occasion for males; ≥ 4 drinks on 1 occasion for females) remains a common high-risk behavior among adolescents (particularly college students). Based on the Monitoring the Future Survey, 1 in 6 high school seniors reported binge drinking in the past 2 weeks.¹³ While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.¹³

While historically more common among males, rates of binge drinking are now basically similar between male and female adolescents.

The National Institute on Alcohol Abuse and Alcoholism has a screening and intervention guide specifically for adolescents.¹⁶A 2-question screening tool asking about personal use of alcohol and use of alcohol by friends is followed by a risk assessment with recommendations to advise young patients not to drink and to assist them with appropriate intervention and follow-up (https://pubs.niaaa.nih.gov/publications/Practitioner/YouthGuide/YouthGuidePocket.pdf).

Illicit drug use. Half of adolescents report using an illicit drug by their senior year in high school.¹³ Marijuana is the most commonly used substance, and laws governing its use are rapidly changing across the United States. Marijuana is illegal in 10 states and legal in 10 states (and the District of Columbia). The remaining states have varying policies on the medical use of marijuana and the decriminalization of marijuana. In addition, cannabinoid (CBD) products are increasingly available. Frequent cannabis use in adolescence has an adverse impact on general executive function (compared with adult users) and learning.¹⁷ Marijuana may serve as a gateway drug in the abuse of other substances,¹⁸ and its use should be strongly discouraged in adolescents.

Of note, there has been a sharp rise in the illicit use of prescription drugs, particularly opioids, creating a public health emergency across the United States.¹⁹ In 2015, more than 4000 young people, ages 15 to 24, died from a drug-related overdose (> 50% of these attributable to opioids).²⁰ Adolescents with a history of substance abuse and behavioral illness are at particular risk. Many adolescents who misuse opioids and other prescription drugs obtain them from friends and relatives.²¹

The Substance Abuse and Mental Health Services Administration (SAMHSA) recommends universal screening of adolescents for substance abuse. This screening should be accompanied by a brief intervention to prevent, mitigate, or eliminate substance use, or a referral to appropriate treatment sources. This process of screening, brief intervention, and referral to treatment (SBIRT) is recommended as part of routine health care.²²

Continue to: Obesity and physical activity

Obesity and physical activity

The percentage of overweight and obese adolescents in the United States has more than tripled over the past 40 years,²³ and 1 in 5 US adolescents is obese.²³ Obese teens are at higher risk for multiple chronic diseases, including type 2 diabetes, sleep apnea, and heart disease.²⁴ They are also more likely to be bullied and to have poor self-esteem.²⁵ Only 1 in 5 American high school students engages in 60 or more minutes of moderate-to-­vigorous physical activity on 5 or more days per week.²⁶

Regular physical activity is, of course, beneficial for cardiorespiratory fitness, bone health, weight control, and improved indices of behavioral health.²⁶ Adolescents who are physically active consistently demonstrate better school attendance and grades.¹⁷ Higher levels of physical fitness are also associated with improved overall cognitive performance.²⁴

General recommendations. The Department of Health and Human Services recommends that adolescents get at least 60 minutes of mostly moderate physical activity every day.²⁶ Encourage adolescents to engage in vigorous physical activity (heavy breathing, sweating) at least 3 days a week. As part of their physical activity patterns, adolescents should also engage in muscle-­strengthening and bone-strengthening activities on at least 3 days per week.

Behavioral health

As young people develop their sense of personal identity, they also strive for independence. It can be difficult, at times, to differentiate normal adolescent rebellion from true mental illness. An estimated 17% to 19% of adolescents meet criteria for mental illness, and about 7% have a severe psychiatric disorder.²⁷ Only one-third of adolescents with mental illness receive any mental health services.²⁸

Depression. The 1-year incidence of major depression in adolescents is 3% to 4%, and the lifetime prevalence of depressive symptoms is 25% in all high school students.²⁷ Risk factors include ethnic minority status, poor self-esteem, poor health, recent personal crisis, insomnia, and alcohol/­substance abuse. Depression in adolescent girls is correlated with becoming sexually active at a younger age, failure to use contraception, having an STI, and suicide attempts. Depressed boys are more likely to have unprotected intercourse and participate in physical fights.²⁹ Depressed teens have a 2- to 3-fold greater risk for behavioral disorders, anxiety, and attention-deficit/hyperactivity disorder (ADHD).³⁰

Continue to: Suicide

Suicide. Among individuals 15 to 29 years of age, suicide is the second leading cause of death globally, with an annual incidence of 11 to 15 per 100,000.³¹ Suicide attempts are 10 to 20 times more common than completed suicide.³¹ Males are more likely than females to die by suicide,³² and boys with a history of attempted suicide have a 30-fold increased risk of subsequent successful suicide.³¹ Hanging, drug poisoning, and firearms (particularly for males) are the most common means of suicide in adolescents. More than half of adolescents dying by suicide have coexisting depression.³¹

Adolescents prefer that providers address sexual health and are more likely to respond if asked directly about sexual behaviors.

Characteristics associated with suicidal behaviors in adolescents include impulsivity, poor problem-solving skills, and dichotomous thinking.³¹ There may be a genetic component as well. In 1 of 5 teenage suicides, a precipitating life event such as the break-up of a relationship, cyber-bullying, or peer rejection is felt to contribute.³¹

ADHD. The prevalence of ADHD is 7% to 9% in US school-aged children.³³ Boys more commonly exhibit hyperactive behaviors, while girls have more inattention. Hyperactivity often diminishes in teens, but inattention and impulsivity persist. Sequelae of ADHD include high-risk sexual behaviors, motor vehicle accidents, incarceration, and substance abuse.³⁴ Poor self-esteem, suicidal ideation, smoking, and obesity are also increased.³⁴ ADHD often persists into adulthood, with implications for social relationships and job performance.³⁴

Eating disorders. The distribution of eating disorders is now known to increasingly include more minorities and males, the latter representing 5% to 10% of cases.³⁵ Eating disorders show a strong genetic tendency and appear to be accelerated by puberty. The most common eating disorder (diagnosed in 0.8%-14% of teens) is eating disorder not otherwise specified (NOS).³⁵ Anorexia nervosa is diagnosed in 0.5% of adolescent girls, and bulimia nervosa in 1% to 2%—particularly among athletes and performers.³⁵ Unanticipated loss of weight, amenorrhea, excessive concern about weight, and deceleration in height/weight curves are potential indicators of an eating disorder. When identified, eating disorders are best managed by a trusted family physician, acting as a coordinator of a multidisciplinary team.

Sexual health

Girls begin to menstruate at an average age of 12, and it takes about 4 years for them to reach reproductive maturity.³⁶ Puberty has been documented to start at younger ages over the past 30 years, likely due to an increase in average body mass index and a decrease in levels of physical activity.³⁷ Girls with early maturation are often insecure and self-conscious, with higher levels of psychological distress.³⁸ In boys, the average age for spermarche (first ejaculation) is 13.³⁹ Boys who mature early tend to be taller, be more confident, and express a good body image.⁴⁰ Those who have early puberty are more likely to be sexually active or participate in high-risk behaviors.⁴¹

Continue to: Pregnancy and contraception

Over the past several decades, more US teens have been abstaining from sexual intercourse or have been using effective forms of birth control, particularly condoms and long-acting reversible contraceptives (LARCs).⁴² Teenage birth rates in girls ages 15 to 19 have declined significantly since the 1980s.⁴² Despite this, the teenage birth rate in the United States remains higher than in other industrialized nations, and most teen pregnancies are unintended.⁴³ Disparities in teenage birth rates also persist across racial and socioeconomic lines.⁴⁴

Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.

There are numerous interventions to reduce teen pregnancy, including sex education, contraceptive counseling, the use of mobile apps that track a user’s monthly fertility cycle or issue reminders to take oral contraceptives,⁴⁵ and the liberal distribution of contraceptives and condoms. The Contraceptive CHOICE Project shows that providing free (or low-cost) LARCs influences young women to choose these as their preferred contraceptive method.⁴⁶ Other programs specifically empower girls to convince partners to use condoms and to resist unwanted sexual advances or intimate partner violence.

Adolescents prefer to have their health care providers address the topic of sexual health. Teens are more likely to share information with providers if asked directly about sexual behaviors.⁴⁷TABLE 2^4,5 offers tips for anticipatory guidance and potential ways to frame questions with adolescents in this context. State laws vary with regard to the ability of minors to seek contraception, pregnancy testing, or care/screening for STIs without parental consent. Contraceptive counseling combined with effective screening decrease the incidence of STIs and pelvic inflammatory disease for sexually active teens.⁴⁸

Sexually transmitted infections

Young adolescents often have a limited ability to imagine consequences related to specific actions. In general, there is also an increased desire to engage in experimental behaviors as an expression of developing autonomy, which may expose them to STIs. About half of all STIs contracted in the United States occur in individuals 15 to 24 years of age.⁴⁹ Girls are at particular risk for the sequelae of these infections, including cervical dysplasia and infertility. Many teens erroneously believe that sexual activities other than intercourse decrease their risk of contracting an STI.⁵⁰

Human papillomavirus (HPV) infection is the most common STI in adolescence.⁵¹ In most cases, HPV is transient and asymptomatic. Oncogenic strains may cause cervical cancer or cancers of the anogenital or oropharyngeal systems. Due to viral latency, it is not recommended to perform HPV typing in men or in women younger than 30 years of age; however, Pap tests are recommended every 3 years for women ages 21 to 29. Primary care providers are pivotal in the public health struggle to prevent HPV infection.

Continue to: Universal immunization of all children...

Universal immunization of all children older than 11 years of age against HPV is strongly advised as part of routine well-child care. Emphasize the proven role of HPV vaccination in preventing cervical⁵² and oropharyngeal⁵³ cancers. And be prepared to address concerns raised by parents in the context of vaccine safety and the initiation of sexual behaviors (www.cdc.gov/hpv/hcp/answering-questions.html).

Chlamydia is the second most common STI in the United States, usually occurring in individuals younger than 24.⁵⁴ The CDC estimates that more than 3 million new chlamydial infections occur yearly. These infections are often asymptomatic, particularly in females, but may cause urethritis, cervicitis, epididymitis, proctitis, or pelvic inflammatory disease. Indolent chlamydial infection is the leading cause of tubal infertility in women.⁵⁴ Routine annual screening for chlamydia is recommended for all sexually active females ≤ 25 years (and for older women with specific risks).⁵⁵ Annual screening is also recommended for men who have sex with men (MSM).⁵⁵

Chlamydial infection may be diagnosed with first-catch urine sampling (men or women), urethral swab (men), endocervical swab (women), or self-collected vaginal swab. Nucleic acid amplification testing is the most sensitive test that is widely available.⁵⁶ First-line treatment includes either azithromycin (1 g orally, single dose) or doxycycline (100 mg orally, twice daily for 7 days).⁵⁶

Gonorrhea. In 2018, there were more than 500,000 annual cases of gonorrhea, with the majority occurring in those between 15 and 24 years of age.⁵⁷ Gonorrhea may increase rates of HIV infection transmission up to 5-fold.⁵⁷ As more adolescents practice oral sex, cases of pharyngeal gonorrhea (and oropharyngeal HPV) have increased. Symptoms of urethritis occur more frequently in men. Screening is recommended for all sexually active women younger than 25.⁵⁶ Importantly, the organism Neisseria gonorrhoeae has developed significant antibiotic resistance over the past decade. The CDC currently recommends dual therapy for the treatment of gonorrhea using 250 mg of intramuscular ceftriaxone and 1 g of oral azithromycin.⁵⁶

Syphilis. Rates of syphilis are increasing among individuals ages 15 to 24.⁵¹ Screening is particularly recommended for MSM and individuals infected with HIV. Benzathine penicillin G, 50,000 U/kg IM, remains the treatment of choice.⁵⁶

Continue to: HIV

HIV. Globally, HIV impacts young people disproportionately. HIV infection also facilitates infection with other STIs. In the United States, the highest burden of HIV infection is borne by young MSM, with prevalence among those 18 to 24 years old varying between 26% to 30% (black) and 3% to 5.5% (non-Hispanic white).⁵¹ The use of emtricitabine/tenofovir disoproxil fumarate for pre-exposure prophylaxis (PrEP) has recently been approved for the prevention of HIV. PrEP reduces risk by up to 92% for MSM and transgender women.⁵⁸

Sexual identity

One in 10 high school students self-identifies as “nonheterosexual,” and 1 in 15 reports same-sex sexual contact.⁵⁹ The term LGBTQ+ includes the communities of lesbian, gay, bisexual, transgender, transsexual, queer, questioning, intersex, and asexual individuals. Developing a safe sense of sexual identity is fundamental to adolescent psychological development, and many adolescents struggle to develop a positive sexual identity. Suicide rates and self-harm behaviors among ­LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.⁶⁰ Rates of mood disorders, substance abuse, and high-risk sexual behaviors are also increased in the LGBTQ+ population.⁶¹

Suicide rates and self-harm behaviors among LGBTQ+ adolescents can be 4 times higher than among their heterosexual peers.

The LGBTQ+ community often seeks health care advice and affirmation from primary care providers. Resources to enhance this care are available at www.lgbthealtheducation.org.

Social media

Adolescents today have more media exposure than any prior generation, with smartphone and computer use increasing exponentially. Most (95%) teens have access to a smartphone,⁶² 45% describe themselves as constantly connected to the Internet, and 14% feel that social media is “addictive.”⁶² Most manage their social media portfolio on multiple sites. Patterns of adolescents' online activities show that boys prefer online gaming, while girls tend to spend more time on social networking.⁶²

Whether extensive media use is psychologically beneficial or deleterious has been widely debated. Increased time online correlates with decreased levels of physical activity.⁶³ And sleep disturbances have been associated with excessive screen time and the presence of mobile devices in the bedroom.⁶⁴ The use of social media prior to bedtime also has an adverse impact on academic performance—particularly for girls. This adverse impact on academics persists after correcting for daytime sleepiness, body mass index, and number of hours spent on homework.⁶⁴

Continue to: Due to growing concerns...

Due to growing concerns about the risks of social media in children and adolescents, the American Academy of Pediatrics has developed the Family Media Plan (www.healthychildren.org/English/media/Pages/default.aspx). Some specific questions that providers may ask are outlined in TABLE 3.⁶⁴ The Family Media Plan can provide age-specific guidelines to assist parents or caregivers in answering these questions.

Cyber-bullying. One in 3 adolescents (primarily female) has been a victim of cyber-bullying.⁶⁵ Sadly, 1 in 5 teens has received some form of electronic sexual solicitation.⁶⁶ The likelihood of unsolicited stranger contact correlates with teens’ online habits and the amount of information disclosed. Predictors include female sex, visiting chat rooms, posting photos, and disclosing personal information. Restricting computer use to an area with parental supervision or installing monitoring programs does not seem to exert any protective influence on cyber-bullying or unsolicited stranger contact.⁶⁵ While 63% of cyber-bullying victims feel upset, embarrassed, or stressed by these contacts,⁶⁶ few events are actually reported. To address this, some states have adopted laws adding cyber-bullying to school disciplinary codes.

Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.

Negative health impacts associated with cyber-bullying include anxiety, sadness, and greater difficulty in concentrating on school work.⁶⁵ Victims of bullying are more likely to have school disciplinary actions and depression and to be truant or to carry weapons to school.⁶⁶ Cyber-bullying is uniquely destructive due to its ubiquitous presence. A sense of relative anonymity online may encourage perpetrators to act more cruelly, with less concern for punishment.

Young people are also more likely to share passwords as a sign of friendship. This may result in others assuming their identity online. Adolescents rarely disclose bullying to parents or other adults, fearing restriction of Internet access, and many of them think that adults may downplay the seriousness of the events.⁶⁶

CORRESPONDENCE
Mark B. Stephens, MD, Penn State Health Medical Group, 1850 East Park Avenue, State College, PA 16803; mstephens3@pennstatehealth.psu.edu.

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

Children born to mothers in poor cardiovascular health during pregnancy had an almost eight times higher risk for landing in the poorest cardiovascular health category in early adolescence than children born to mothers who had ideal cardiovascular health during pregnancy.

Doug Brunk/MDedge News

In an observational cohort study that involved 2,302 mother-child dyads, 6.0% of mothers and 2.6% of children were considered to be in the poorest category of cardiovascular health on the basis of specific risk factors.

The children of mothers with any “intermediate” cardiovascular health metrics in pregnancy – for example, being overweight but not obese – were at just more than two times higher risk for poor cardiovascular health in early adolescence.

Although acknowledging the limitations of observational data, Amanda M. Perak, MD, Northwestern University, Chicago, suggested that focusing on whether or not the relationships seen in this study are causal might be throwing the baby out with the bathwater.

“I would suggest that it may not actually matter whether there is causality or correlation here, because if you can identify newborns at birth who have an eight times higher risk for poor cardiovascular health in childhood based on mom’s health during pregnancy, that’s valuable information either way,” said Dr. Perak.

“Even if you don’t know why their risk is elevated, you might be able to target those children for more intensive preventative efforts throughout childhood to help them hold on to their cardiovascular health for longer.”

That said, she thinks it’s possible that the intrauterine environment might actually directly affect offspring health, either through epigenetics modifications to cardiometabolic regulatory genes or possibly through actual organ development. Her group is collecting epigenetic data to study this further.

“We also need to do a study to see if intervening during pregnancy with mothers leads to better cardiovascular health in offspring, and that’s a question we can answer with a clinical trial,” said Dr. Perak.

This study was published on Feb. 16, 2021, in JAMA.
 

Equal footing

“We’ve always talked about cardiovascular health as if everyone is born with ideal cardiovascular health and loses it from there, and I think what this article points out is that not everybody starts on equal footing,” said Stephen R. Daniels, MD, PhD, University of Colorado at Denver, Aurora, who wrote an editorial accompanying the study.

“We need to start upstream, working with mothers before and during pregnancy, but it’s also important to understand, from a pediatric standpoint, that with some of these kids the horse is kind of already out of the barn very early.”

Dr. Daniels is pediatrician in chief and chair of pediatrics at Children’s Hospital Colorado in Aurora.

This study is the first to examine the relevance of maternal gestational cardiovascular health to offspring cardiovascular health and an important first step toward developing new approaches to address the concept of primordial prevention, he said.

“If primary prevention is identifying risk factors and treating them, I think of primordial prevention as preventing the development of those risk factors in the first place,” said Dr. Daniels.

Future trials, he added, should focus on the various mechanistic pathways – biological effects, shared genetics, and lifestyle being the options – to better understand opportunities for intervention.
 

Mother-child pairs

Dr. Perak and colleagues used data from the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study and the HAPO Follow-up Study.

Participants were 2,302 mother-child pairs from nine field centers in Barbados, Canada, China, Thailand, United Kingdom, and the United States, and represented a racially and ethnically diverse cohort.

The mean ages were 29.6 years for pregnant mothers and 11.3 years for children. The pregnancies occurred between 2000 and 2006, and the children were examined from 2013 to 2016, when the children were aged 10-14 years.

Using the American Heart Association’s definition of cardiovascular health, the scientists categorized pregnancy health for mothers based on their measures of body mass index, blood pressure, total cholesterol, glucose level, and smoking status at 28 weeks’ gestation. These five metrics of gestational cardiovascular health have been significantly associated with adverse pregnancy outcomes.

They categorized cardiovascular health for offspring at age 10-14 years based on four of these five metrics: body mass index, blood pressure, cholesterol, and glucose.

Only 32.8% of mothers and 42.2% of children had ideal cardiovascular health.

In analyses adjusted for pregnancy and birth outcomes, the associations seen between poor gestational maternal health and offspring cardiovascular health persisted but were attenuated.

Dr. Perak reported receiving grants from the Woman’s Board of Northwestern Memorial Hospital; the Dixon Family; the American Heart Association; and the National Heart, Lung, and Blood Institute. Dr. Daniels reported no conflicts of interest.

A version of this article first appeared on Medscape.com.

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

A version of this article first appeared on Medscape.com.

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

A version of this article first appeared on Medscape.com.

The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.

South_agency/Getty Images

The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.

The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.

“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.

“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.

“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
 

Results contrast with Pfizer trials of vaccine

The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.

Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.

“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.

Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.

However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.

“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
 

Findings reported in British newspapers

The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.

The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”

Most make the point that there were only 26 people with obesity among the 248 persons in the study.

“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.

“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.
 

Antibody responses differ by BMI, age, and sex

In the Italian study, the participants – 158 women and 90 men – were assigned to receive a priming BNT162b2 vaccine dose with a booster at day 21. Blood and nasopharyngeal swabs were collected at baseline and 7 days after the second vaccine dose.

After the second dose, 99.5% of participants developed a humoral immune response; one person did not respond. None tested positive for SARS-CoV-2.

Titers of SARS-CoV-2–binding antibodies were greater in younger than in older participants. There were statistically significant differences between those aged 37 years and younger (453.5 AU/mL) and those aged 47-56 years (239.8 AU/mL; P = .005), those aged 37 years and younger versus those older than 56 years (453.5 vs 182.4 AU/mL; P < .0001), and those aged 37-47 years versus those older than 56 years (330.9 vs. 182.4 AU/mL; P = .01).

Antibody response was significantly greater for women than for men (338.5 vs. 212.6 AU/mL; P = .001).

Humoral responses were greater in persons of normal-weight BMI (18.5-24.9 kg/m2; 325.8 AU/mL) and those of underweight BMI (<18.5 kg/m2; 455.4 AU/mL), compared with persons with preobesity, defined as BMI of 25-29.9 (222.4 AU/mL), and those with obesity (BMI ≥30; 167.0 AU/mL; P < .0001). This association remained after adjustment for age (P = .003).

“Our data stresses the importance of close vaccination monitoring of obese people, considering the growing list of countries with obesity problems,” the researchers noted.

Hypertension was also associated with lower antibody titers (P = .006), but that lost statistical significance after matching for age (P = .22).

“We strongly believe that our results are extremely encouraging and useful for the scientific community,” Dr. Pellini and colleagues concluded.

The authors disclosed no relevant financial relationships. Dr. Iwasaki is a cofounder of RIGImmune and is a member of its scientific advisory board.

This article was updated on 3/8/21.

A version of this article first appeared on Medscape.com.

EVIDENCE SUMMARY

Metformin has modest effects on body weight

A large systematic review and meta-­analysis (38 RCTs; n = 2199) published in 2020 evaluated metformin therapy in children and adolescents (including those with metabolic disease, growth problems, and psychological disorders in addition to obesity and overweight).¹ Over an average of 6 months, metformin use modestly reduced BMI (weighted mean difference [WMD] = –1.07 kg/m²; 95% CI, –1.43 to –0.72 kg/m²) and body weight (WMD = –2.51 kg; 95% CI, –3.14 to –1.89 kg) for all participants.¹

However, the authors also performed a meta-analysis of trials involving obese or overweight youth without other comorbidities. Participants in these trials ranged in age from 7 to 17 years (mean not supplied; most trials, 12-15 years), had a BMI greater than the 95th percentile for age, and took doses of metformin ranging from 1500 to 3000 mg (most trials, 1500-2000 mg/d for 24 weeks).¹ In this analysis, metformin reduced body weight (8 trials; n = 616; WMD = –2.06 kg; 95% CI, –3.47 to –0.65 kg) and body fat mass (–1.9%; 95% CI, –3.25% to –0.56%). But it did not reduce BMI (12 trials; n = 826; WMD = –0.76 kg/m²; 95 % CI, –1.61 to 0.08 kg/m²) or improve lean body mass (2 trials; N = 98; WMD = –0.74 kg; 95% CI, –2.4 to 0.91 kg).¹

The authors of this meta-analysis did not include an evaluation of the quality of the individual RCTs.

Metformin has benefits but also adverse effects

A 2016 Cochrane systematic review and ­meta-analysis assessed 8 trials (total n = 543) evaluating metformin vs placebo in adolescents prescribed exercise and lifestyle support.² This meta-analysis included 4 trials (n = 294) with obese or overweight adolescents that were also included in the newer meta-analysis,¹ as well as 4 trials involving obese adolescents with insulin resistance. The authors did not assess the effects of metformin on obese or overweight adolescents separately.

Over 6 months, metformin use reduced BMI (WMD = –1.35 kg/m²; 95% CI –2 to –0.69 kg/m²).² Metformin commonly produced gastrointestinal symptoms: diarrhea, flatulence (rates not given), and nausea in 15% to 42% compared with 3% to 21% with placebo (no comparison statistic supplied), however rarely to the point of discontinuation (< 5%).² Nine participants withdrew due to adverse effects: 5 in the metformin group and 4 in the placebo group. The authors rated the quality of the included trials as low to moderate.

An evidence report and systematic review (42 RCTs; total n = 6956) compared the efficacy of several approaches for weight loss in adolescents, including metformin (6 of the 8 RCTs included in the 2020 meta-analysis¹) and lifestyle interventions.³ Interventions comprising exercise and diet counseling for > 26 hours over 6 to 12 months produced decreases in BMI (–0.86 kg/m²; 95% CI –1.44 to –0.29 kg/m²) but not weight (–2 kg; 95% CI –3.2 to 1.2 kg).³

Recommendations from others

The US Preventive Services Task Force states that metformin treatment in adolescents who are overweight or obese produces a small reduction in BMI when compared to placebo, but the clinical significance of this reduction is unclear.³

Editor’s takeaway

The idea of using medications for weight loss remains seductive, given how hard it can be for patients to achieve significant, lasting weight loss through lifestyle modification. Evidence suggests that metformin can help in this regard but not enough to recommend it. In addition, metformin therapy is associated with gastrointestinal adverse effects.

EVIDENCE SUMMARY

Metformin has modest effects on body weight

A large systematic review and meta-­analysis (38 RCTs; n = 2199) published in 2020 evaluated metformin therapy in children and adolescents (including those with metabolic disease, growth problems, and psychological disorders in addition to obesity and overweight).¹ Over an average of 6 months, metformin use modestly reduced BMI (weighted mean difference [WMD] = –1.07 kg/m²; 95% CI, –1.43 to –0.72 kg/m²) and body weight (WMD = –2.51 kg; 95% CI, –3.14 to –1.89 kg) for all participants.¹

However, the authors also performed a meta-analysis of trials involving obese or overweight youth without other comorbidities. Participants in these trials ranged in age from 7 to 17 years (mean not supplied; most trials, 12-15 years), had a BMI greater than the 95th percentile for age, and took doses of metformin ranging from 1500 to 3000 mg (most trials, 1500-2000 mg/d for 24 weeks).¹ In this analysis, metformin reduced body weight (8 trials; n = 616; WMD = –2.06 kg; 95% CI, –3.47 to –0.65 kg) and body fat mass (–1.9%; 95% CI, –3.25% to –0.56%). But it did not reduce BMI (12 trials; n = 826; WMD = –0.76 kg/m²; 95 % CI, –1.61 to 0.08 kg/m²) or improve lean body mass (2 trials; N = 98; WMD = –0.74 kg; 95% CI, –2.4 to 0.91 kg).¹

The authors of this meta-analysis did not include an evaluation of the quality of the individual RCTs.

Metformin has benefits but also adverse effects

A 2016 Cochrane systematic review and ­meta-analysis assessed 8 trials (total n = 543) evaluating metformin vs placebo in adolescents prescribed exercise and lifestyle support.² This meta-analysis included 4 trials (n = 294) with obese or overweight adolescents that were also included in the newer meta-analysis,¹ as well as 4 trials involving obese adolescents with insulin resistance. The authors did not assess the effects of metformin on obese or overweight adolescents separately.

Over 6 months, metformin use reduced BMI (WMD = –1.35 kg/m²; 95% CI –2 to –0.69 kg/m²).² Metformin commonly produced gastrointestinal symptoms: diarrhea, flatulence (rates not given), and nausea in 15% to 42% compared with 3% to 21% with placebo (no comparison statistic supplied), however rarely to the point of discontinuation (< 5%).² Nine participants withdrew due to adverse effects: 5 in the metformin group and 4 in the placebo group. The authors rated the quality of the included trials as low to moderate.

An evidence report and systematic review (42 RCTs; total n = 6956) compared the efficacy of several approaches for weight loss in adolescents, including metformin (6 of the 8 RCTs included in the 2020 meta-analysis¹) and lifestyle interventions.³ Interventions comprising exercise and diet counseling for > 26 hours over 6 to 12 months produced decreases in BMI (–0.86 kg/m²; 95% CI –1.44 to –0.29 kg/m²) but not weight (–2 kg; 95% CI –3.2 to 1.2 kg).³

Recommendations from others

The US Preventive Services Task Force states that metformin treatment in adolescents who are overweight or obese produces a small reduction in BMI when compared to placebo, but the clinical significance of this reduction is unclear.³

Editor’s takeaway

The idea of using medications for weight loss remains seductive, given how hard it can be for patients to achieve significant, lasting weight loss through lifestyle modification. Evidence suggests that metformin can help in this regard but not enough to recommend it. In addition, metformin therapy is associated with gastrointestinal adverse effects.

EVIDENCE SUMMARY

Metformin has modest effects on body weight

A large systematic review and meta-­analysis (38 RCTs; n = 2199) published in 2020 evaluated metformin therapy in children and adolescents (including those with metabolic disease, growth problems, and psychological disorders in addition to obesity and overweight).¹ Over an average of 6 months, metformin use modestly reduced BMI (weighted mean difference [WMD] = –1.07 kg/m²; 95% CI, –1.43 to –0.72 kg/m²) and body weight (WMD = –2.51 kg; 95% CI, –3.14 to –1.89 kg) for all participants.¹

However, the authors also performed a meta-analysis of trials involving obese or overweight youth without other comorbidities. Participants in these trials ranged in age from 7 to 17 years (mean not supplied; most trials, 12-15 years), had a BMI greater than the 95th percentile for age, and took doses of metformin ranging from 1500 to 3000 mg (most trials, 1500-2000 mg/d for 24 weeks).¹ In this analysis, metformin reduced body weight (8 trials; n = 616; WMD = –2.06 kg; 95% CI, –3.47 to –0.65 kg) and body fat mass (–1.9%; 95% CI, –3.25% to –0.56%). But it did not reduce BMI (12 trials; n = 826; WMD = –0.76 kg/m²; 95 % CI, –1.61 to 0.08 kg/m²) or improve lean body mass (2 trials; N = 98; WMD = –0.74 kg; 95% CI, –2.4 to 0.91 kg).¹

The authors of this meta-analysis did not include an evaluation of the quality of the individual RCTs.

Metformin has benefits but also adverse effects

A 2016 Cochrane systematic review and ­meta-analysis assessed 8 trials (total n = 543) evaluating metformin vs placebo in adolescents prescribed exercise and lifestyle support.² This meta-analysis included 4 trials (n = 294) with obese or overweight adolescents that were also included in the newer meta-analysis,¹ as well as 4 trials involving obese adolescents with insulin resistance. The authors did not assess the effects of metformin on obese or overweight adolescents separately.

Over 6 months, metformin use reduced BMI (WMD = –1.35 kg/m²; 95% CI –2 to –0.69 kg/m²).² Metformin commonly produced gastrointestinal symptoms: diarrhea, flatulence (rates not given), and nausea in 15% to 42% compared with 3% to 21% with placebo (no comparison statistic supplied), however rarely to the point of discontinuation (< 5%).² Nine participants withdrew due to adverse effects: 5 in the metformin group and 4 in the placebo group. The authors rated the quality of the included trials as low to moderate.

An evidence report and systematic review (42 RCTs; total n = 6956) compared the efficacy of several approaches for weight loss in adolescents, including metformin (6 of the 8 RCTs included in the 2020 meta-analysis¹) and lifestyle interventions.³ Interventions comprising exercise and diet counseling for > 26 hours over 6 to 12 months produced decreases in BMI (–0.86 kg/m²; 95% CI –1.44 to –0.29 kg/m²) but not weight (–2 kg; 95% CI –3.2 to 1.2 kg).³

Recommendations from others

The US Preventive Services Task Force states that metformin treatment in adolescents who are overweight or obese produces a small reduction in BMI when compared to placebo, but the clinical significance of this reduction is unclear.³

Editor’s takeaway

The idea of using medications for weight loss remains seductive, given how hard it can be for patients to achieve significant, lasting weight loss through lifestyle modification. Evidence suggests that metformin can help in this regard but not enough to recommend it. In addition, metformin therapy is associated with gastrointestinal adverse effects.

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com

Metformin has a modest favorable effect on body mass index z score and insulin resistance in children and adolescents with obesity, compared with placebo, according to a systematic review of trial data.

moodboard/thinkstockphotos

“The available evidence is of varying quality,” however, and the drug increases the likelihood of gastrointestinal adverse effects, reported Reem Masarwa, PharmD, PhD, and colleagues in Pediatrics. “Nonetheless, metformin may be considered for use as a pharmacologic therapy in this pediatric population because of its modest efficacy, availability, cost, and safety profile.”

The Food and Drug Administration has approved metformin for the treatment of type 2 diabetes in children and adolescents. Doctors have used the drug off label for weight loss in children with obesity, but this use “remains controversial,” the review authors said.

To assess the efficacy and safety of metformin plus lifestyle interventions compared with placebo plus lifestyle interventions in children and adolescents with obesity, Dr. Masarwa, with the Center for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, and the department of epidemiology, biostatistics, and occupational health, McGill University, Montreal, and colleagues systematically reviewed data from randomized controlled trials (RCTs). Their review was published online in Pediatrics.

The investigators focused on studies that examined outcomes such as body mass index, BMI z score, insulin resistance, and gastrointestinal adverse effects. They excluded studies of children with type 2 diabetes.

The researchers included 24 RCTs in their review. The studies included 1,623 children and adolescents who received metformin (861 participants) or placebo (762 participants). Indications included uncomplicated obesity in 10 studies, obesity with insulin resistance in 9 studies, prediabetes in 3 studies, and nonalcoholic fatty liver disease in 2 studies. One of the trials did not incorporate a lifestyle cointervention.

Participants ranged in age from 4 years to 19 years, and trial durations ranged from 2 months to 2 years. The total daily dose of metformin ranged from 500 mg to 2,000 mg.

In 14 RCTs that reported BMI, metformin generally decreased BMI (range of mean changes: –2.70 to 1.30), compared with placebo (range of mean changes: –1.12 to 1.90), although three trials suggested that metformin increased BMI. The average difference in the treatment effect between the metformin and placebo groups ranged from –2.72 to 0.70. “Importantly, the authors of many RCTs reported variable treatment effects, preventing definitive conclusions from being drawn from individual trials,” Dr. Masarwa and coauthors wrote.

In seven RCTs that reported BMI z score, metformin consistently decreased BMI z score (range of mean changes: –0.37 to –0.03), compared with placebo (range of mean changes: –0.22 to 0.15). The mean difference in the treatment effect between treatment groups ranged from –0.15 to –0.07. The largest decrease occurred in patients with nonalcoholic fatty liver disease.

The rate of gastrointestinal adverse events nearly doubled with metformin treatment, relative to placebo (rate range: 2%-74% for metformin vs. 0%-42% for placebo).

Metformin adherence rates ranged from 60% to 90%, and lifestyle cointerventions varied substantially across the trials, the researchers noted. The clinical significance and long-term effects of metformin treatment in this population “remain uncertain,” they said.
 

Off-label use may not be ideal

“Ideally, children with obesity should be entered into a clinical trial rather than placed on an off-label medication,” Vandana Raman, MD, and Carol M. Foster, MD, said in a related commentary. Still, treatment with metformin may be reasonable in certain cases, said Dr. Raman and Dr. Foster of the division of endocrinology in the department of pediatrics at the University of Utah in Salt Lake City. “Metformin is a low-cost option and may provide modest clinical benefit for weight loss with minimal side effects. If lifestyle modification has been pursued but has achieved minimal weight loss, it may be reasonable to try an agent such as metformin as adjunctive therapy,” they said.

Lifestyle modification therapy – including nutritional changes, physical activity, and behavior modification – has been the “mainstay of management” for patients with obesity, and this approach underpins successful weight loss, they said. But durable weight loss with lifestyle modification may be challenging, and pharmacologic treatments “are attractive options before proceeding to bariatric surgery,” they said.

For younger patients, FDA-approved medications for obesity include orlistat and liraglutide for patients aged 12 years and older, and phentermine for patients aged 16 years and older.

“Orlistat has been associated with modest BMI reduction but may cause intolerable gastrointestinal side effects and possible fat-soluble vitamin deficiency,” they said. “Phentermine is approved for short-term therapy only and may increase heart rate and blood pressure and cause irritability and insomnia.”

Liraglutide, which was approved for the treatment of pediatric obesity in December 2020, reduced BMI in a trial that included adolescents with obesity. About 43% of the participants who received liraglutide, compared with 18% who received placebo, had a 5% reduction in BMI. In addition, 26% and 8%, respectively, had a 10% reduction in BMI. The use of liraglutide “is limited by the need for daily subcutaneous injections and high frequency of gastrointestinal side effects and high cost,” however, the commentary authors noted.

In addition, the FDA has approved setmelanotide for children older than 6 years with obesity caused by three rare genetic conditions.

Some small studies have suggested that topiramate may lead to meaningful weight loss in children, but the medication has been associated with cognitive dysfunction, they said.
 

Considering surgery

“This is an important review of the efficacy of metformin as a tool for weight loss in children with obesity,” said Suzanne C. Boulter, MD, adjunct professor emeritus of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H. “Results showed modest decreases in BMI z scores compared to placebo but there were a significant percentage of GI side effects and dropouts from the trials.”

“Tools other than lifestyle changes are needed to address” pediatric obesity, Dr. Boulter said. “Another tool is gastric bypass which is now a recommended intervention in selected clinical sites for adolescents 14 years of age and older with BMIs greater than 35.”

Dr. Boulter highlighted a recent study in Pediatrics that examined data from more than 200 adolescents who underwent bariatric surgery. The researchers found that outcomes were similar for older and younger patients.

“It would be interesting to pediatricians in practice to see a comparison study between metformin and bariatric surgery long-term results,” Dr. Boulter added.

Dr. Masarwa and coauthors received support from the Quebec Foundation for Health Research and the Canadian Institutes of Health Research Drug Safety and Effectiveness Cross-Disciplinary Training Program. One coauthor also is supported by an award from McGill University.

The authors of the systematic review and the accompanying commentary had no relevant financial disclosures. Dr. Boulter is a member of the editorial advisory board for Pediatric News and had no relevant financial disclosures.

jremaly@mdedge.com

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Patients with severe asthma and comorbid atopy, obesity, and depression/anxiety had fewer annual exacerbations after receiving mepolizumab, according to research from the annual meeting of the American Academy of Allergy, Asthma, and Immunology.

“Mepolizumab has clearly been shown to improve severe asthma control in many clinical trials, but atopy, obesity, and depression/anxiety affect patients with asthma at an increased rate,” Thomas B. Casale, MD, former AAAAI president and professor of medicine and pediatrics at the University of South Florida in Tampa, said in a presentation at the meeting. “Yet, few studies have examined whether asthma therapy with these comorbidities works.”

Dr. Casale and colleagues performed a retrospective analysis of patients in the United States from the MarketScan Commercial and Medicare Supplemental Database between November 2014 and December 2018 who had atopy, obesity, or depression/anxiety in addition to asthma and were receiving mepolizumab. Atopy in the study was defined as allergic rhinitis, anaphylaxis, atopic dermatitis, conjunctivitis, eosinophilic esophagitis, and food allergies. Patients were at least age 12 years, had at least one diagnosis for asthma, at least one diagnosis code for atopic disease, obesity, or depression/anxiety at baseline, and at least two administrations of mepolizumab within 180 days.

The researchers examined the number of exacerbations, oral corticosteroid (OCS) claims, and OCS bursts per year at 12-month follow-up, compared with baseline. They identified exacerbations by examining patients who had an emergency department or outpatient claim related to their asthma, and a claim for systemic corticosteroids made in the 4 days prior to or 5 days after a visit, or if their inpatient hospital admission contained a primary asthma diagnosis. Dr. Casale and colleagues measured OCS bursts as a pharmacy claim of at least 20 mg of prednisone per day for between 3 and 28 days plus a claim for an emergency department visit related to asthma in the 7 days prior or 6 days after the claim.

At baseline, patients across all groups were mean age 50.5-52.4 years with a Charleson Comorbidity Index score between 1.1 and 1.4, a majority were women (59.0%-72.0%) and nearly all were commercially insured (88.0%-90.0%). Patients who used biologics at baseline and/or used a biologic that wasn’t mepolizumab during the follow-up period were excluded.

Medication claims in the groups included inhaled corticosteroids (ICS) (36.8%-48.6%), ICS/long-acting beta-agonist (LABA) (60.2%-63.0%), LABA/ long-acting muscarinic antagonist (LAMA) (1.2%-3.5%), ICS/LABA/LAMA (21.2%-25.1%), short-acting beta-agonist (SABA) (83.2%-87.7%), LAMA alone (33.5%-42.1%), or leukotriene receptor antagonist (LTRA).

In the non–mutually exclusive group of patients with atopy (468 patients), 28.0% had comorbid obesity and 26.0% had comorbid depression/anxiety. For patients with obesity categorized in a non–mutually exclusive subgroup (171 patients), 79.0% had comorbid atopy and 32.0% had comorbid depression/anxiety. Among patients with non–mutually exclusive depression/anxiety (173 patients), 70.0% had comorbid atopy, while 32.0% had comorbid obesity.

The results showed the mean number of overall exacerbations decreased by 48% at 12 months in the atopic group (2.3 vs. 1.2; P < .001), 52% in the group with obesity (2.5 vs. 1.2; P < .001), and 38% in the depression/anxiety group (2.4 vs. 1.5; P < .001). The mean number of exacerbations leading to hospitalizations decreased by 64% in the atopic group (0.11 vs. 0.04; P < .001), 65% in the group with obesity (0.20 vs. 0.07; P < .001), and 68% in the group with depression/anxiety (0.22 vs. 0.07; P < .001).

The researchers also found the mean number of OCS claims and OCS bursts also significantly decreased over the 12-month follow-up period. Mean OCS claims decreased by 33% for patients in the atopic group (5.5 vs. 3.7; P < .001), by 38% in the group with obesity (6.1 vs. 3.8; P < .001), and by 31% in the group with depression/anxiety (6.2 vs. 4.3; P < .001).

The mean number of OCS bursts also significantly decreased by 40% in the atopic group (2.0 vs. 2.1; P < .001), 48% in the group with obesity (2.3 vs. 1.2; P < .001), and by 37% in the group with depression/anxiety (1.9 vs. 1.2; P < .001). In total, 69% of patients with comorbid atopy, 70.8% of patients with comorbid obesity, and 68.2% of patients with comorbid depression/anxiety experienced a mean decrease in their OCS dose over 12 months.

“These data demonstrate that patients with asthma and atopy, obesity, or depression and anxiety have significantly fewer exacerbations and reduced OCS use in a real-world setting with treatment of mepolizumab,” Dr. Casale said. “Thus, holistic patient care for severe asthma is critical, and mepolizumab provides tangible clinical benefit despite the complexities of medical comorbidities.”

This study was funded by GlaxoSmithKline, and the company also funded graphic design support of the poster. Dr. Casale reports he has received research funds from GlaxoSmithKline. Four authors report being current or former GlaxoSmithKline employees; three authors report holding stock and/or shares of GlaxoSmithKline. Three authors are IBM Watson Health employees, a company GlaxoSmithKline has provided research funding.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

Girls with more body fat experienced earlier menarche and hormone changes, but later full breast development, compared with those with normal weight, according to longitudinal data from 90 girls aged 8-15 years.

A link between obesity and early puberty has been observed among U.S. girls for decades, but more recent studies suggest that “girls with greater childhood adiposity have earlier thelarche and progress through puberty at a faster rate than normal weight girls,” wrote Madison T. Ortega, MD, of the National Institute of Environmental Health Sciences, Durham, N.C., and colleagues. However, studies involving hormone levels have yielded mixed results, they said.

In a study published in the Journal of Clinical Endocrinology & Metabolism , the researchers followed 36 girls with overweight or obesity and 54 girls with normal weight for 4 years; normal weight was defined as body mass index in the 5th to 85th percentile, overweight was defined as BMI in the 85th to 95th percentile, and obese was defined as greater than 95th percentile. Overweight and obese were combined into one category for comparison with normal weight girls.

Participants had an average of 2.8 study visits during this period and provided additional information by phone and online. Visits included measurement of total body fat using dual-energy x-ray absorptiometry (DXA), Tanner staging, breast ultrasound for morphological staging (BMORPH; A-E), pelvic ultrasound, hormone tests, and menarchal status assessment.

Overall, girls with overweight/obesity (OW/OB) had significantly more advanced breast development at baseline than did those with normal weight (NW), but these girls progressed through BMORPH stage D later than did NW girls. Early-stage breast development was not affected by total body fat. However, “an increase of 5 percentage points in mean total body fat, for example, was associated with a 26% decrease in the transition rate out of stage D,” the researchers noted.

Hormone levels were similar at baseline for follicle-stimulating hormone, inhibin B, estrone (E1), total and free testosterone, and androstenedione. However, these levels increased more quickly after 1 year for girls with OW/OB, while they plateaued in girls with NW and dropped among girls with lower total body fat. Total body fat had no apparent effect on other reproductive hormones including luteinizing hormone, modified vaginal maturation index, and estradiol 2.

The average age of menarche was 12.4 years across all participants, but girls with higher total body fat at baseline were more likely to reach menarche at a younger age. “For every 1-unit increase in visit one total body fat, the chance of achieving menarche at any given time point was 3% higher,” the researchers said. No interaction appeared between race and total body fat with regard to menarche.


 

Several surprising findings

The study is important because “there have been no longitudinal studies in U.S. girls to examine how total body fat affects serum reproductive hormones or the development of the breast and ovaries using ultrasound imaging,” corresponding author Natalie Shaw, MD, of the National Institute of Environmental Health Sciences, said in an interview.

Dr. Shaw said she was surprised by several of the study findings. “Others have reported increased male-like hormones (androgens) in overweight/obese girls in cross-sectional studies; however, we were surprised to find that FSH and inhibin B were also elevated in girls with excess body fat,” she said. “We also found, unexpectedly, that even though the breast bud appears earlier in overweight/obese girls (thelarche), which signals the onset of puberty, the breast matured more slowly during the course of puberty in overweight/obese girls compared with normal weight girls,” she noted.

“The main take-home message is that puberty looks different in girls with excess body fat; they develop breast tissue earlier, yet take longer to achieve a fully mature breast, and they undergo menarche earlier,” Dr. Shaw said. Clinicians should be aware of the hormonal differences based on body fat, Dr. Shaw emphasized. “Girls with greater body fat had higher levels of FSH (a pituitary hormone), inhibin B (an ovarian hormone), and male-like reproductive hormones (e.g., testosterone) that are made by the adrenal glands and the ovaries in the late stages of puberty,” she said.
 

Potential implications for adulthood

“The findings in this study contribute to better understanding how total body fat impacts hormonal findings of puberty,” M. Susan Jay, MD, of the Medical College of Wisconsin and Children’s Hospital of Wisconsin, Milwaukee, said in an interview. “Prior studies have linked weight gain as a factor that contributes to pubertal development, but this study is attempting to longitudinally investigate how body weight may affect clinical and biochemical pubertal markers in girls,” she noted.

“The take-home message is that this study and other earlier studies have illustrated that puberty is not a fixed pattern in all individual girls,” Dr. Jay emphasized. “Rather, there are environmental factors which can impact pubertal course,” she said. “In effect, there are pathways through puberty in individual adolescents that require greater ongoing studies to further identify the arc of puberty and the impact of how the length in various stages may affect exposure to estrogen and other neurohormonal factors,” she explained. These factors impact not only adolescence but also future health in adulthood, she said.

“Ongoing prospective studies are needed to identify how factors such as body weight can affect adolescent pubertal development and the possible impact long after adolescence for health issues such as breast cancer,” Dr. Jay added.

The study findings were limited by several factors including the available data from only two completed study visits for most participants, as well as the racial differences among body weight groups and lack of standardized timing for blood draws, the researchers noted.

The study was supported in part by the National Institute of Environmental Health Sciences, and corresponding author Dr. Shaw disclosed support as a Lasker Clinical Research Scholar. The other researchers, as well as Dr. Jay, had no disclosures.

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

A version of this article first appeared on Medscape.com.

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

A version of this article first appeared on Medscape.com.

Roughly 40% of all U.S. cases of incident diabetes during 2013-2016 were directly attributable to obesity, a finding that further solidifies the major etiologic role for obesity in the current American diabetes epidemic.

Researchers used data from a diverse cohort of 4,200 American adults in the MESA study during 2000-2017 to calculate a relative risk for developing diabetes of 2.7 in people with obesity compared with similar participants without obesity.

They then applied this relative risk estimate to obesity prevalence rates during serial iterations of NHANES, the recurring U.S.-wide survey of vital statistics in a representative cross-sectional population.

Their calculations showed that, during 2013-2016, 41% of U.S. adults who developed new onset diabetes did so because of obesity, after the researchers adjusted for potential confounders.

This “population attributable fraction,” or disease burden attributable to obesity, varied somewhat by sex, and by racial and ethnic subgrouping. Obesity was linked with the highest attributable rate among non-Hispanic White women, a rate of 53%, and with the lowest rate among non-Hispanic Black men, with an attributable fraction of 30%, Natalie A. Cameron, MD, and colleagues reported in their study, published online Feb. 10 in the Journal of the American Heart Association.
 

Potential for “meaningful impact” by reducing obesity

“Our study highlights the meaningful impact that reducing obesity could have on type 2 diabetes prevention in the United States. Decreasing obesity needs to be a priority,” Dr. Cameron, of the McGaw Medical Center of Northwestern University in Chicago, said in a statement issued by the American Heart Association.

“Public health efforts that support healthy lifestyles, such as increasing access to nutritious foods, promoting physical activity, and developing community programs to prevent obesity, could substantially reduce new cases of type 2 diabetes,” she added.

MESA (Multi-Ethnic Study of Atherosclerosis) enrolled adults aged 45-84 years and free from clinical cardiovascular disease at six U.S. sites during 2000-2002, and then followed them with four additional examinations through 2017.

For the current study, researchers narrowed the cohort down to 4,200 participants who were aged 45-79 years and free from diabetes at entry, and also restricted this subgroup to participants classified as non-Hispanic White (54% of the cohort), non-Hispanic Black (33%), or Mexican American (13%). At entry, 34% of the cohort had obesity, with a body mass index of at least 30 kg/m².

During a median follow-up of just over 9 years, 12% of the cohort developed incident diabetes. After adjustment for possible confounders, a hazard ratio model showed an overall 2.7-fold higher rate of incident diabetes among people with obesity compared to those without.

The researchers then applied this hazard ratio to obesity prevalence statistics from NHANES (National Health and Nutrition Examination Survey) during the same time period, with data from the biennial NHANES project collapsed into four time strata: 2001-2004, 2005-2008, 2009-2012, and 2013-2016. They again limited their analysis to NHANES data collected from people aged 45-79 years who self-reported categorization as non-Hispanic White, non-Hispanic Black, or Mexican American.

During the period from 2001-2004 to 2013-2016, overall obesity prevalence tallied by NHANES data rose from 34% to 41%. Among people with type 2 diabetes during 2013-2016, obesity prevalence was 65%.

To calculate the population attributable fraction researchers combined the MESA and NHANES estimates and adjusted for potential confounders and found that, overall, in 41% of people with incident diabetes during 2013-2016, the disease was attributable to obesity.

The study received no commercial funding, and none of the authors had disclosures.

A version of this article first appeared on Medscape.com.

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

A version of this article first appeared on Medscape.com.

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

A version of this article first appeared on Medscape.com.

The phase 3a STEP 1 trial that investigated the use of semaglutide (Novo Nordisk), a glucagonlike peptide–1 (GLP-1) agonist, for weight loss is aptly named, some say.

“In sum, we have a long way to go to control the obesity epidemic ... but on the face of it, the STEP 1 trial (like its name) is a good beginning,” wrote coeditorialists Julie R. Ingelfinger, MD, from Harvard Medical School, Boston, and a deputy editor of the New England Journal of Medicine, and Clifford J. Rosen, MD, from Tufts University School of Medicine, also in Boston.

The trial findings by John P.H. Wilding, DM, University of Liverpool (England), and colleagues and an accompanying editorial were published online Feb. 10, 2021, in the New England Journal of Medicine.

“The results are encouraging, with significantly more patients in the semaglutide group having clinically important weight loss,” Dr. Ingelfinger and Dr. Rosen stressed.

However, they also cautioned that “despite the positive results of this trial, the present study has some important limitations” and “there are concerns, including adverse events (mostly gastrointestinal – nausea, sometimes vomiting, and diarrhea) related primarily to the class of the agent.”

Two U.K. experts drew similar takeaways, speaking to the U.K. Science Media Centre.

“This was a well-designed study with unequivocal findings,” which showed that semaglutide “is indeed likely to be a game-changer in the fight against obesity,” according to Baptiste Leurent, PhD, London School of Hygiene and Tropical Medicine.

However, if the drug is approved at this dose for this use, patients would need close monitoring for gastrointestinal disorders, and “we also need to better understand what is happening once the treatment is stopped, and whether it could be taken for a shorter period of time.”

Sir Stephen O’Rahilly, MD, MRC Metabolic Diseases Unit, University of Cambridge (England), pointed out that “GLP-1 is made by cells in the intestine and levels increase in the blood after a meal, providing some of the signal to the brain that tells us we are ‘full,’ ” so GLP-1 agonists have been studied as appetite suppressants, in addition to their approved use to treat type 2 diabetes.

Only about 4.5% of participants in STEP 1 stopped taking semaglutide because of gastrointestinal issues, he noted, although more participants in that group reported problems with gallstones, which can follow rapid weight loss.

And “unlike some previous appetite suppressant drugs which caused significant psychological and psychiatric side effects, there is no evidence that semaglutide has any adverse effects of that nature,” Dr. O’Rahilly noted.

In sum, he said, “this is the start of a new era for obesity drug development with the future direction being to achieve levels of weight loss comparable to semaglutide, while having fewer side effects.”
 

‘Pressing need’ to address obesity; semaglutide filed for obesity

There is a “pressing need” to address the worldwide increase in obesity and weight-related coexisting conditions, Dr. Ingelfinger and Dr. Rosen noted.

Sustained long-term weight loss with diet and exercise is challenging; behavioral weight-loss strategies “fail more often than not,” bariatric surgery is invasive and often followed by eventual weight regain, they wrote.

In addition, said Dr. Wilding and colleagues, the “use of available [weight-loss] medications remains limited by modest efficacy, safety concerns, and cost.”

Subcutaneous semaglutide, approved for treating type 2 diabetes (as Ozempic) in adults at doses of up to 1 mg/week, induced weight loss at higher doses. The current study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) that aimed to test the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.

Topline results from STEP 1 were presented June 4, 2020.

And as reported earlier, results from STEP 3 – a 68-week trial of semaglutide versus placebo in 611 participants who all received very intensive diet and exercise counseling – were presented at the virtual ObesityWeek 2020 meeting.

The four trials of semaglutide for weight loss have been completed and the data were submitted to the Food and Drug Administration on Dec. 4, 2020 (with a decision expected within 6 months) and to the European Medicines Agency on Dec. 18, 2020.
 

Most patients had 5% weight loss with semaglutide

The STEP 1 trial enrolled 1,961 adults with a body mass index (BMI) of at least 30 kg/m² or at least 27 with at least one weight-related coexisting condition, but without type 2 diabetes, at 129 sites in 16 countries in Asia, Europe, North America, and South America.

Participants were a mean age of 47 and three-quarters were women. Most participants were White (76%), followed by Asian (13%), Black or African American (6%), or other (5%).

On average, they had a BMI of 38 and weighed 105 kg. Three-quarters had one or more coexisting conditions.

Participants were randomized to receive semaglutide (1,306 patients) or placebo (655 patients), added to lifestyle intervention.

Everyone received 17 monthly individual counseling sessions during which they learned about adhering to a diet with a 500-calorie/day deficit, were encouraged to build up to walking 150 minutes each week, and recorded their daily diet and exercise (in a diary or using an app).

Semaglutide was administered with a prefilled pen injector at a dose of 0.25 mg/week for the first 4 weeks, escalated to 2.4 mg/week by week 16 (or lower if the patient had unacceptable side effects).

At 68 weeks, participants in the semaglutide versus placebo group had greater mean weight loss (14.9% vs. 2.4%, or 15.3 kg vs. 2.6 kg).

Participants in the semaglutide versus placebo group were much more likely to have lost at least 5% of their initial weight (86% vs. 31.5%) or at least 10% of their initial weight (69.1% vs. 12.0%), or at least 15% of their initial weight (50.5% vs. 4.9%; P < .001 for all three comparisons).

About 80% of participants adhered to the study treatment. A third of participants in the semaglutide group who completed the study lost at least 20% of their initial weight, which approaches the 20%-30% reported weight loss 1-3 years after sleeve gastrectomy, the researchers noted.

Participants in the semaglutide group also had greater improvements in waist circumference and levels of hemoglobin A1c, C-reactive protein (a marker of inflammation), and fasting lipids, as well as in physical function scores on SF-36 and IWQOL-Lite-CT questionnaires.

In their editorial, Dr. Ingelfinger and Dr. Rosen noted that “daily oral semaglutide [already approved in 7-mg and 14-mg doses for the treatment of type 2 diabetes as Rybelsus] might be more appealing to many people,” as a weight-loss medication than a once-weekly subcutaneous dose. Semaglutide is the first GLP-1 agonist available as an oral agent.

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial (with expected completion in 2023) will shed light on cardiovascular outcomes after 2.5-5 years.
 

GI disorders and ‘important limitations’

More participants in the semaglutide than the placebo group reported gastrointestinal disorders (typically nausea, diarrhea, vomiting, and constipation; 74.2% vs. 47.9%), which were mostly transient and mild to moderate in severity, but also led to more treatment discontinuation (7.0% vs. 3.1%).

More patients in the semaglutide versus placebo group had a gall bladder–related disorder (2.6% vs. 1.2%, mostly cholelithiasis) and mild acute pancreatitis (3 vs. 0 participants), but there were no between-group differences in neoplasms.

Dr. Wilding and colleagues acknowledge the limitations of the study, including the fact that it enrolled mainly women, mainly non-White participants, was relatively short, and excluded patients with type 2 diabetes.

Mean placebo-corrected weight loss with 2.4 mg/weekly subcutaneous semaglutide was greater than with 3.0 mg once-daily subcutaneous liraglutide (Saxenda, Novo Nordisk) – the only GLP-1 agonist approved for weight management – in the 56-week SCALE trial (12.4% vs. 4.5%); however, the two studies had different populations.

The study was supported by Novo Nordisk. Dr. Ingelfinger is a deputy editor and Dr. Rosen is an associate editor of the New England Journal of Medicine. Dr. Ingelfinger, Dr. Rosen, and Dr. Leurent have reported no relevant financial relationships. Dr. O’Rahilly has a current research collaboration with Novo Nordisk scientists in an unrelated area and has been a consultant for the company.

A version of this article first appeared on Medscape.com.

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.
 

Patients who received intensive lifestyle training by coaches in the primary care setting experienced improvement in several indicators of cardiometabolic health in a 2-year trial.

The 803 trial participants comprised a racially diverse, low-income population with obesity. In this study, primary care clinics were randomly assigned to provide weight-loss coaching or usual care. Patients at the intensive training clinics lost significantly more weight than the other patients, as reported in a paper published in September in the New England Journal of Medicine on the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) trial. The patients who received weight loss coaching also had significantly more improvement in HDL cholesterol levels, total to HDL cholesterol ratios, and metabolic syndrome severity score, said researchers in the new paper on the PROPEL trial, which was published in Circulation on February 8 .

“We believe that one reason for success of the program was the use of a health coach [who] was embedded in the primary care office,” said lead author Peter Katzmarzyk, PhD, associate executive director for population and public health sciences at the Pennington Biomedical Research Center, Baton Rouge, La. “This way, the patients could get their counseling in a familiar environment and did not have to go to a different setting. The coaches developed close relationships with the patients over the 2 years, and this helped develop a sense of responsibility in the patients as the coaches were helping the patients to set goals and kept them accountable.”

In the PROPEL study, 67% of patients were Black and had low health literacy scores that corresponded with less than a ninth-grade education level. The intensive lifestyle intervention program included weekly sessions with the trained health coaches over the first 6 months — 16 face-to-face and 6 over the phone — and then at least monthly for the last 18 months. The coaches had higher education degrees in nutrition, physical activity, or behavioral medicine. Before the program started, the coaches also received training in the management of obesity and related health issues, health literacy, and patient communication and education. The goal of the program was 10% weight loss, using personalized action plans on eating, dieting, and physical activity.

Those in the usual-care clinics continued receiving normal care and received newsletters on health topics, such as the importance of sleep and tips for limiting time spent sitting. The primary care physicians at those clinics also were given a presentation with Centers for Medicare & Medicaid Services (CMS) information on intensive lifestyle interventions for obesity.
 

Cholesterol changes in intervention vs. control group

HDL cholesterol improved significantly among the coached patients, compared with the other patients, with a mean difference of 4.1 mg/dL at 1 year and 4.6 mg/dL at 2 years (P less than .01 for both). The total cholesterol to HDL cholesterol ratio showed a similarly significant difference in decline, with a between-group difference of –0.29 at 1 year and –0.31 at 2 years (P less than .01 for both). Also, the difference in the change in metabolic severity scores were –0.40 at 1 year and –0.21 at 2 years (P less than .01 for both).

Fasting blood glucose had declined after the 1st year by a significantly greater degree in the clinics with coaching, compared with the others, but not after the second year, researchers found.

There were no significant differences seen in total cholesterol, LDL cholesterol, non-HDL cholesterol, or blood pressure. Dr. Katzmarzyk said the likely reason for no change in blood pressure was that it was already relatively well-controlled at baseline for all the patients.
 

Funding barriers to obesity treatment

The CMS currently cover intensive training for obesity if delivered directly by a primary care physician, according to the authors of the new paper. Dr. Katzmarzyk said he hopes that will change.

“We are hoping that the evidence provided in this study may change the way that CMS funds obesity treatment in the future by allowing an expansion of the care team,” he said.

John Flack, MD, chair of internal medicine at Southern Illinois University, Springfield, said that the main achievement of the study was that it showed that intensive weight-loss training in the primary-care setting could be accomplished in a racially diverse population with low health literacy.

“You can’t just automatically assume just because you’ve seen it in some other populations that you can replicate this in every population, so they’ve done a really good job,” he said.

That programs are eligible for reimbursement only if they’re run by primary-care physicians is an ongoing problem, he said.

“You don’t necessarily need to be a physician to do this,” Dr. Flack said.

For best results, payment for coaching should not be tied to office visits, Dr. Flack noted.

“If they’re de-tethered from the office visits and you’re paid for quality ... you’re going to build out your infrastructure differently to care for people,” he said.

Andrew Freeman, MD, associate professor of medicine at the University of Colorado, Denver, and cochair of the American College of Cardiology’s nutrition and lifestyle work group, said the findings dovetail with his experience.

“I’m a huge believer that when people need to make lifestyle changes, having someone hold their hand and guide them through the effort is incredibly rewarding and incredibly powerful,” said Dr. Freeman, who also oversees the intensive cardiac rehab program at National Jewish Health in Denver.

A program like this needs proper funding in order to work, Dr, Freeman noted. He added that, even with coaches being paid well, “if you are able to prevent just one readmission for, say, heart failure a month . . . you could be saving millions of dollars over just a couple of years.”

Dr. Katzmarzyk, Dr. Flack, and Dr. Freeman reported no relevant disclosures. Louisiana State University, Pennington Biomedical Research Center, and Montclair State University have interest in the intellectual property surrounding a weight graph used in the study. The other researchers reported grants and/or fees from Bayer, Boehringer Ingelheim, Gilead, Takeda, Novo Nordisk, and other companies.