Obesity

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

Bariatric surgery can reduce the risk of long-term cardiovascular outcomes in older Medicare beneficiaries with obesity, a large new observational study in which a third of the patients were over age 65 years suggests.

Overall, patients who underwent bariatric surgery had 37% lower all-cause mortality and were significantly less likely to have admissions for new-onset heart failure (64% risk reduction), myocardial infarction (37% risk reduction), and ischemic stroke (29% risk reduction), compared with similar patients who received more conservative treatment, after a median of 4 years of follow-up, report Amgad Mentias, MD, MS, a clinical cardiologist at the Cleveland Clinic Foundation, Ohio, and colleagues.

The results were published in the Journal of the American College of Cardiology.

Previous studies on bariatric surgery outcomes have primarily focused on individuals from select health care networks or medical facilities with restricted coverage in the United States or on patients with diabetes, noted Tiffany M. Powell-Wiley, MD, MPH, of the National Institutes of Health’s National Heart, Lung, and Blood Institute, Bethesda, Maryland, and colleagues in an accompanying editorial.

Contemporary cohort of patients

“A lot of the studies showed long-term outcomes outside of the U.S., specifically in Europe,” Dr. Mentias added.

The aim of this study was to evaluate the long-term association between bariatric surgery and risk of adverse cardiovascular outcomes in a contemporary large cohort from the United States.

Older patients (> 65 years) and those without diabetes were looked at as specific subgroups.

The researchers assessed 189,770 patients. There were 94,885 matched patients in each cohort. Mean age was 62.33 years. Female patients comprised 70% of the cohort. The study group had an average BMI of 44.7 kg/m2.

The study cohort was matched 1:1. Participants were either part of a control group with obesity or a group of Medicare beneficiaries who had bariatric surgery between 2013 and 2019. Sex, propensity score matching on 87 clinical variables, age, and BMI were used to match patients.

Myocardial infarction, new-onset heart failure, ischemic stroke, and all-cause mortality were all study outcomes. As a sensitivity analysis, the study team conducted an instrumental variable assessment.

More specifically, the findings showed that bariatric surgery was linked with the following after a median follow-up of 4.0 years:

• Myocardial infarction (hazard ratio, 0.63; 95% confidence interval, 0.59-0.68)
• Stroke (HR, 0.71; 95% CI, 0.65-0.79)
• New-onset heart failure (HR, 0.46; 95% CI, 0.44-0.49)
• Reduced risk of death (9.2 vs. 14.7 per 1000 person-years; HR, 0.63; 95% CI, 0.60-0.66)

Findings for those over the age of 65 were similar – lower risks of all-cause mortality (HR, 0.64), new-onset heart failure (HR, 0.52), myocardial infarction (HR, 0.70), and stroke (HR, 0.76; all P < .001). Similar findings were shown in subgroup analyses in men and women and in patients with and without diabetes.

The study cohort primarily consisted of Medicare patients, which limits the generalizability of the data. Lack of data on medications taken for cardiovascular and weight loss purposes and potential coding errors because the information was gathered from an administrative database were all limitations of the study, the researchers note.

An additional limitation was that residual unmeasured confounders, particularly patient-focused physical, social, and mental support factors, could play a role in whether a patient opted to have bariatric surgery, the study authors note.

“Additional studies are needed to compare cardiovascular outcomes after bariatric surgery with weight loss medications like glucagon-like peptide-1 (GLP-1) analogues,” the researchers add.

This study was partially funded by philanthropic contributions by the Khouri family, Bailey family, and Haslam family to the Cleveland Clinic for co-author Dr. Milind Y. Desai’s research. Dr. Mentias has disclosed no relevant financial relationships. Dr. Powell-Wiley disclosed relationships with the National Institute on Minority Health and Health Disparities and the Division of Intramural Research of the National, Heart, Lung, and Blood Institute of the National Institutes of Health.

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

Reports of long waiting times at mental health clinics and anecdotal observations by health care providers suggest the pandemic has generated a dramatic increase in the incidence of eating disorders among the pediatric population. Of course this should come as no surprise to pediatricians.

Eating disorders come in many different forms and a triggering event is sometimes difficult to define. Often the adolescent or preadolescent is searching for some sense of stability in a life tossed on a stormy sea roiled by hormonal and physical change. Wresting control of their bodies during a period of uncertainty may result in a downward spiral into dangerously unhealthy weight loss. If nothing else, the pandemic has been a period of dramatic uncertainty unlike what most children and few adults in this country have ever experienced.

With the unprecedented increase in eating disorder cases, providers in several disciplines are searching for novel strategies to ease the burden on their patients and their practices. I recently learned of a pediatric practice in California that is considering blinding all patients aged 12 and older to the body mass measurements obtained at their health maintenance visits.

Blind weight checks for children with eating disorders, particularly those who seem to be nearing recovery, has been a common and often helpful practice. However, I am unaware of any practice that has made it a universal office policy. I’m unsure of the rationale behind this practice’s policy, but on several fronts, suppressing body mass measurements in the age group most vulnerable to eating disorders makes some sense.

Universal blind weight checks could minimize the risk of in-office shaming. However, careful training of support staff and thoughtful placement of the scales could serve the same purpose. This new policy acknowledges not only the ubiquity of the problem but also that many, maybe even most, children with eating disorders appear normal. And of course, there is the unfortunate fact that body mass is a poor screening test for eating disorders.

As I thought more about this novel approach I came to see its educational value for patients, parents, and even physicians. I can envision how a 13-year-old’s first health maintenance visit would go after the roll-out of the new policy. “Dr. Smith, aren’t you going to tell us how much I (or my daughter Jenny) weigh(s)?” This could, or more likely, should launch a discussion about weight and body image. It might continue with questions like, “How much do you think you weigh?” Or, “Do you think you are too heavy or too thin?”

Or, the conversation could include the provider’s observations that weight is just one measure of health and in fact not a very good one. Other ingredients in a healthy life style, such as sleep and physical activity, are not as easy to measure as weight but in many cases are more important.

As my mind struggled to restructure a health maintenance schedule that included blind weight checks, I wondered why we should wait until age 12. Of course, it is unreasonable to expect parents to stick with a pediatric practice that seems to ignore their infant’s weight. I’m sure that, like me, you have always discouraged new parents from having a baby scale at home because in the first few months too-frequent weighings can usually cause more angst than good.

It might make sense to remove a within-earshot discussion of a child’s weight from the health maintenance visit as soon as the child can absorb and digest the discussion; say, around age 3 years. In a perfect world, the provider should have already elicited a history that suggested a young child’s vulnerability to obesity before the scale and the growth chart told the unfortunate story. But, neither you nor I are perfect providers and so we will always need the scale to document our concerns. However, when and how we report that one vital sign to the patient and his or her parents is a topic ripe for discussion and improvement.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Reports of long waiting times at mental health clinics and anecdotal observations by health care providers suggest the pandemic has generated a dramatic increase in the incidence of eating disorders among the pediatric population. Of course this should come as no surprise to pediatricians.

Eating disorders come in many different forms and a triggering event is sometimes difficult to define. Often the adolescent or preadolescent is searching for some sense of stability in a life tossed on a stormy sea roiled by hormonal and physical change. Wresting control of their bodies during a period of uncertainty may result in a downward spiral into dangerously unhealthy weight loss. If nothing else, the pandemic has been a period of dramatic uncertainty unlike what most children and few adults in this country have ever experienced.

With the unprecedented increase in eating disorder cases, providers in several disciplines are searching for novel strategies to ease the burden on their patients and their practices. I recently learned of a pediatric practice in California that is considering blinding all patients aged 12 and older to the body mass measurements obtained at their health maintenance visits.

Blind weight checks for children with eating disorders, particularly those who seem to be nearing recovery, has been a common and often helpful practice. However, I am unaware of any practice that has made it a universal office policy. I’m unsure of the rationale behind this practice’s policy, but on several fronts, suppressing body mass measurements in the age group most vulnerable to eating disorders makes some sense.

Universal blind weight checks could minimize the risk of in-office shaming. However, careful training of support staff and thoughtful placement of the scales could serve the same purpose. This new policy acknowledges not only the ubiquity of the problem but also that many, maybe even most, children with eating disorders appear normal. And of course, there is the unfortunate fact that body mass is a poor screening test for eating disorders.

As I thought more about this novel approach I came to see its educational value for patients, parents, and even physicians. I can envision how a 13-year-old’s first health maintenance visit would go after the roll-out of the new policy. “Dr. Smith, aren’t you going to tell us how much I (or my daughter Jenny) weigh(s)?” This could, or more likely, should launch a discussion about weight and body image. It might continue with questions like, “How much do you think you weigh?” Or, “Do you think you are too heavy or too thin?”

Or, the conversation could include the provider’s observations that weight is just one measure of health and in fact not a very good one. Other ingredients in a healthy life style, such as sleep and physical activity, are not as easy to measure as weight but in many cases are more important.

As my mind struggled to restructure a health maintenance schedule that included blind weight checks, I wondered why we should wait until age 12. Of course, it is unreasonable to expect parents to stick with a pediatric practice that seems to ignore their infant’s weight. I’m sure that, like me, you have always discouraged new parents from having a baby scale at home because in the first few months too-frequent weighings can usually cause more angst than good.

It might make sense to remove a within-earshot discussion of a child’s weight from the health maintenance visit as soon as the child can absorb and digest the discussion; say, around age 3 years. In a perfect world, the provider should have already elicited a history that suggested a young child’s vulnerability to obesity before the scale and the growth chart told the unfortunate story. But, neither you nor I are perfect providers and so we will always need the scale to document our concerns. However, when and how we report that one vital sign to the patient and his or her parents is a topic ripe for discussion and improvement.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

Reports of long waiting times at mental health clinics and anecdotal observations by health care providers suggest the pandemic has generated a dramatic increase in the incidence of eating disorders among the pediatric population. Of course this should come as no surprise to pediatricians.

Eating disorders come in many different forms and a triggering event is sometimes difficult to define. Often the adolescent or preadolescent is searching for some sense of stability in a life tossed on a stormy sea roiled by hormonal and physical change. Wresting control of their bodies during a period of uncertainty may result in a downward spiral into dangerously unhealthy weight loss. If nothing else, the pandemic has been a period of dramatic uncertainty unlike what most children and few adults in this country have ever experienced.

With the unprecedented increase in eating disorder cases, providers in several disciplines are searching for novel strategies to ease the burden on their patients and their practices. I recently learned of a pediatric practice in California that is considering blinding all patients aged 12 and older to the body mass measurements obtained at their health maintenance visits.

Blind weight checks for children with eating disorders, particularly those who seem to be nearing recovery, has been a common and often helpful practice. However, I am unaware of any practice that has made it a universal office policy. I’m unsure of the rationale behind this practice’s policy, but on several fronts, suppressing body mass measurements in the age group most vulnerable to eating disorders makes some sense.

Universal blind weight checks could minimize the risk of in-office shaming. However, careful training of support staff and thoughtful placement of the scales could serve the same purpose. This new policy acknowledges not only the ubiquity of the problem but also that many, maybe even most, children with eating disorders appear normal. And of course, there is the unfortunate fact that body mass is a poor screening test for eating disorders.

As I thought more about this novel approach I came to see its educational value for patients, parents, and even physicians. I can envision how a 13-year-old’s first health maintenance visit would go after the roll-out of the new policy. “Dr. Smith, aren’t you going to tell us how much I (or my daughter Jenny) weigh(s)?” This could, or more likely, should launch a discussion about weight and body image. It might continue with questions like, “How much do you think you weigh?” Or, “Do you think you are too heavy or too thin?”

Or, the conversation could include the provider’s observations that weight is just one measure of health and in fact not a very good one. Other ingredients in a healthy life style, such as sleep and physical activity, are not as easy to measure as weight but in many cases are more important.

As my mind struggled to restructure a health maintenance schedule that included blind weight checks, I wondered why we should wait until age 12. Of course, it is unreasonable to expect parents to stick with a pediatric practice that seems to ignore their infant’s weight. I’m sure that, like me, you have always discouraged new parents from having a baby scale at home because in the first few months too-frequent weighings can usually cause more angst than good.

It might make sense to remove a within-earshot discussion of a child’s weight from the health maintenance visit as soon as the child can absorb and digest the discussion; say, around age 3 years. In a perfect world, the provider should have already elicited a history that suggested a young child’s vulnerability to obesity before the scale and the growth chart told the unfortunate story. But, neither you nor I are perfect providers and so we will always need the scale to document our concerns. However, when and how we report that one vital sign to the patient and his or her parents is a topic ripe for discussion and improvement.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at pdnews@mdedge.com.

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

At least one in four adults worldwide is thought to have nonalcoholic fatty liver disease, a major risk factor for cardiovascular disease (CVD), which is the leading cause of death in NAFLD, but the condition is widely underdiagnosed, according to a new American Heart Association scientific statement on NAFLD and cardiovascular risks.

The statement, published in Arteriosclerosis, Thrombosis, and Vascular Biology, aims to increase awareness of NAFLD among cardiologists and other clinicians treating vulnerable patients. It pulls together the existing evidence for using imaging to diagnose NAFLD as well as the role of current and emerging treatments for managing the disease.

“NAFLD is common, but most patients are undiagnosed,” statement writing committee chair P. Barton Duell, MD, said in an interview. “The identification of normal liver enzyme levels does not exclude the diagnosis of NAFLD. Early diagnosis and treatment are necessary to improve the health of patients with established NAFLD, as well as preventing the development of NAFLD in patients who are at risk for the condition.”

Dr. Duell is a professor at the Knight Cardiovascular Institute and division of endocrinology, diabetes and clinical nutrition at Oregon Health & Science University, Portland.

This is the AHA’s first scientific statement on NAFLD. In 2021, the association issued a statement on obesity and CVD). Also in 2021, a multiorganization group headed by the American Gastroenterological Association published a “Call to Action” on nonalcoholic steatohepatitis (NASH) , a form of NAFLD that’s characterized by inflammation and scarring of the liver, and typically requires a liver biopsy for diagnosis.

Key take-homes

The AHA statement on NAFLD is sweeping. Among its key take-home messages:

• Calling into question the effectiveness of AST and ALT testing for diagnosing NAFLD and NASH.
• Providing context to the role of insulin resistance – either with or without diabetes – as well as obesity (particularly visceral adiposity), metabolic syndrome, and dyslipidemia in NAFLD.
• Advocating for lifestyle interventions – diet, exercise, weight loss and alcohol avoidance – as the key therapeutic intervention for NAFLD.
• Asserting that glucagonlike peptide–1 receptor agonists may modestly improve NAFLD.

The statement also tackles the differences in terminology different organizations use to describe NAFLD. “The terminology section is important to ensure everyone is using the right terminology in assessing patients, as well as choosing appropriate treatment interventions,” Dr. Duell said.

The statement also explores genetic factors that can predispose people to NAFLD, Dr. Duell pointed out, and it goes into detail about strategies for screening NAFLD and NASH. “It is not possible to diagnose NAFLD without understanding the pros and cons of various screening modalities, as well as the lack of sensitivity of some tests for detection of NAFLD We hope this information will increase success in screening for and early identification of NAFLD.”

Dr. Duell explained the rationale for issuing the statement. “Rates of NAFLD are increasing worldwide in association with rising rates of elevated body mass index and the metabolic syndrome, but the condition is commonly undiagnosed,” he said. “This allows patients to experience progression of disease, leading to hepatic and cardiovascular complications.” 

Avoiding NAFLD risk factors along with early diagnosis and treatment “may have the potential to mitigate long-term complications from NAFLD,” Dr. Duell said.

“This is one of first times where we really look at cardiovascular risks associated with NAFLD and pinpoint the risk factors, the imaging tools that can be used for diagnosing fatty liver disease, and ultimately what potential treatments we can consider,” Tiffany M. Powell-Wiley, MD, MPH, author of the AHA statement on obesity and CV risk, said in an interview.

“NAFLD has not been at the forefront of  cardiologists’ minds, but this statement highlights the importance of liver fat as a fat depot,” said Dr. Powell-Wiley, chief of the Social Determinants of Obesity and Cardiovascular Risk Laboratory at the National Heart, Lung, and Blood Institute in Bethesda, Md.

“It does provide greater clarity for us as cardiologists, especially when thinking about what is required for diagnosis and ultimately how this relates to cardiovascular disease for people with fatty liver disease,” she said.

Dr. Duell and Dr. Powell-Wiley have no relevant relationships to disclose.


 

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

A weight-loss program can lead to type 2 diabetes remission, even in individuals with a normal body mass index (BMI), via loss of body fat, particularly in the liver and pancreas, shows a U.K. study.

The ReTUNE trial, funded by Diabetes UK, involved 20 people with type 2 diabetes of less than 6 year’s duration and a BMI of 27 kg/m² or lower.

Joel Austell/MDedge News

After 1 year, participants had lost 9% of their body weight.

Their body fat decreased significantly, to the same level as controls without type 2 diabetes, and they experienced decreases in liver fat, total triglycerides, and pancreatic fat.

The research, presented at the 2022 Diabetes UK Professional Conference, also showed this was accompanied by increases in insulin secretion and reductions in hemoglobin A1c and fasting plasma glucose levels.

Lead author Roy Taylor, MD, PhD, professor of medicine and metabolism, Newcastle University, Newcastle upon Tyne, England, said the findings indicate that the “etiology and pathophysiology of type 2 diabetes is the same whether BMI is normal or raised.”

This information should make a profound difference in what doctors advise their patients, Dr. Taylor added.

“One of the dramatic things about dealing with people in this group,” he said, “is they feel very resentful that healthcare professionals tell them not to lose weight.”

Based on the current results, Dr. Taylor believes this is “inappropriate advice, and it’s that personal advice that I think that this study points a way towards.”
 

Weight loss ‘first line of treatment’

These findings support the theory of a personal fat threshold, above which “type 2 diabetes occurs,” said Dr. Taylor. “Weight loss is the first-line treatment for all with type 2 diabetes, irrespective of BMI.”

Dr. Taylor already showed in the DiRECT trial that a calorie-restricted liquid diet followed by gradual food reintroduction and a weight-loss maintenance program can achieve and sustain type 2 diabetes remission at 2 years in people who are overweight or obese.

As reported this news organization, 36% of 300 patients enrolled in the trial attained diabetes remission and maintained it out to 24 months, compared with negligible changes in the control group.

Inspired by the results of DiRECT and the DROPLET study, the National Health Service has been rolling out a low calorie–diet treatment program for people who are overweight and living with diabetes.

Asked during the postpresentation discussion whether the current results could have implications for the NHS program, Dr. Taylor said it remains, in effect, a study and will not change things for now.

Chris Askew, chief executive of Diabetes UK, said in a release: “This game-changing study ... advances our understanding of why type 2 diabetes develops and what can be done to treat it.

“Our ambition is for as many people as possible to have the chance to put their type 2 diabetes into remission and live well for longer.”

Mr. Askew continued: “The findings of ReTUNE potentially take us a significant step closer to achieving this goal by showing that remission isn’t only possible for people of certain body weights.”
 

Weight and body fat decrease led to remission

For ReTUNE, the team recruited 20 individuals with type 2 diabetes of less than 6 year’s duration who had a BMI of 21-27 and compared them with 20 matched controls, with a follow-up of 52 weeks. 

Patients were an average age of 59.0 years, 13 were women, mean BMI was 24.8, and average duration of diabetes was 2.8 years. Mean A1c was 54 mmol/mol.

Fourteen of the patients were taking metformin at enrollment and two were being treated with gliclazide. These medications were stopped when the individuals with type 2 diabetes entered a weight-loss program incremented in 5% steps, followed by 6 weeks of weight stability.

Overall, weight decreased by an average of 9%, while body fat decreased from 32% at baseline to 28% at 1 year (P < .001), the same percentage as that seen in the controls.

Liver fats also decreased significantly from baseline (P < .001) down to approximately the same level as controls at 1 year, a pattern also seen with very low-density lipoprotein cholesterol and triglyceride levels.

Pancreatic fat decreased steadily and significantly over the course of the 52-week follow-up (P < .05), although remained above the level seen in controls.

Insulin secretion increased significantly over the course of the study (P = .005) to finish just over the threshold for the lower range of normal at 52 weeks.

This, Dr. Taylor showed, was enough for the 14 patients who achieved type 2 diabetes remission to see their A1c levels fall significantly during follow-up (P < .001), alongside fasting plasma glucose levels (P < .001).

ReTUNE is funded by Diabetes UK. The authors reported no relevant financial relationships.

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

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

Pregnant women with even mild hypertension should receive blood pressure–lowering medications to reduce the likelihood of adverse outcomes for the mother and the child, according to a large, open-label, randomized trial.

“Treating to the blood pressure goal in this study reduced the risk of adverse events associated with pregnancy but did not impair fetal growth,” Alan T. Tita, MD, PhD, associate dean for Global and Women’s Health, University of Alabama, Birmingham, reported at the annual scientific sessions of the American College of Cardiology.

The question of whether to treat chronic hypertension during pregnancy has been “an international controversy for decades,” said Dr. Tita, who led the investigator-initiated Chronic Hypertension and Pregnancy (CHAP) trial.

For the composite primary outcome of severe preeclampsia, medically indicated preterm birth at less than 35 weeks of gestation, placental abruption, or fetal/neonatal death, the treatment of hypertension versus no treatment showed a relative risk reduction of 18% (30.2% vs. 37%, (hazard ratio, 0.82; P < .001).
 

Small for gestational age is primary safety endpoint

An increase in preeclampsia risk in women whose fetus was small for gestational age (SGA), a theoretical consequence of reductions in arterial pressure, was not seen. The rate of SGA, defined as below the 10^th percentile, was slightly higher in the treatment group (11.2% vs. 10.4%), but the difference did not approach significance (P = 0.76).

By answering this long-pending question, the CHAP data are “practice changing,” declared an ACC-invited commentator, Athena Poppas, MD, chief of cardiology and director of the Lifespan Cardiovascular Institute, Providence, R.I. She agreed that the need for treatment of mild chronic hypertension has been a dilemma for clinicians that is now acceptably resolved.

In this trial, 2,408 pregnant women with chronic mild hypertension defined as a blood pressure of 160/90 mm Hg were randomized to treatment with a goal blood pressure of less than 140/90 mm Hg or no treatment unless the blood pressure rose to at least 160/105. All women had singleton pregnancies. Enrollment before 23 weeks of gestation was required. Severe hypertension (at least 160/105 mm Hg) was an exclusion criterion, as were several comorbidities, such as kidney disease.
 

Combination therapy accepted for <140/90 mm Hg goal

The beta-blocker labetalol or the calcium channel blocker nifedipine as single agents were the preferred antihypertensive medications in the protocol, but other medications were permitted. To reach the blood pressure goal, the single-agent therapy was titrated to the maximum dose before starting a second agent.

After randomization the systolic and diastolic blood pressures fell in both groups, but they fell more and remained consistently lower in the active treatment group, particularly during the first 20 weeks after randomization, according to graphs displayed by Dr. Tita. Over the course of the study, the mean diastolic blood pressures were 129.5 and 132.6 mm Hg in the active treatment and control groups, respectively, while the systolic pressures were 79.1 vs. 81.5 mm Hg.

When the components of the primary outcome were evaluated separately, the greatest advantage of treatment was the reduction in the rate of severe eclampsia (23.3% vs. 29.1%; HR, 0.80: 95% confidence interval, 0.70-0.92) and preterm birth (12.2% vs. 16.7%; HR, 0.73: 95% CI, 0.60-0.89).

Across a large array of subgroups, including those with or without diabetes and those treated before or after 14 weeks of gestation, there was a consistent advantage for treatment, even if not statistically different. It is notable that 48% of patients were Black and 35% had a body mass index of at least 40. The active treatment was favored across all groups stratified by these characteristics.

Although the incidences of placental abruption (1.7% on treatment vs. 1.9% without) and fetal or neonatal death (3.5% vs. 4.3%) were lower in the active treatment group, they were uncommon events in both arms of the study. The differences did not reach statistical significance.
 

Maternal morbidity rates lower on treatment

Severe SGA, which was defined as below the 5^th percentile, was also numerically but not significantly higher in the control arm than in the group receiving treatment (5.1% vs. 5.5%), but the incidence of composite adverse maternal events was numerically lower (2.1% vs. 2.8%). The incidences of all components of maternal morbidity, such as maternal death (0.1% vs. 0.2%) pulmonary edema (0.4% vs. 0.9%), heart failure (0.1% vs. 0.1%), and acute kidney injury (0.8% vs. 1.2%), were either lower or the same on active treatment versus no treatment.

According to Dr. Tita, who called CHAP one of the largest and most diverse studies to address the value of treating mild hypertension in pregnancy, the American College of Obstetricians and Gynecologists (ACOG) is evaluating these data for changing their current guidelines for managing hypertension during pregnancy.

“The rate of chronic hypertension during pregnancy has been rising in the United States due to the increase in the average age of pregnant women and the rising rates of obesity,” Dr. Tita commented.

“We definitely needed these data,” said Mary Norine Walsh, MD, medical director, Ascension Saint Vincent Cardiovascular Research Institute, Indianapolis. Not only has the value of treating mild hypertension been unresolved, but Dr. Walsh pointed out that the rates of maternal mortality in the United States are rising and now generally exceed those of many other developed countries.

There are several features in the design of this trial that make the results even more salient to clinical practice, according to Dr. Walsh. This includes the fact that about half of patients enrolled were on Medicaid. As a result, the study confirmed benefit in what Dr. Walsh characterized as a “vulnerable” population.

“We will be busy now to make sure that our [pregnant] patients are achieving these target blood pressures,” Dr. Walsh said. She indicated that CHAP validates the treatment target of 140/90 mm Hg as a standard of care.

The results were published in the New England Journal of Medicine simultaneously with its ACC presentation.

The trial was funded by the National Heart, Lung, and Blood Institute. Dr. Tita reports research grants from Pfizer. Dr. Walsh reports a financial relationship with EBR Systems. Dr. Poppas reports no potential conflicts of interest.

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

There is a link between cannabis exposure during pregnancy and higher fasting glucose levels and adiposity in the offspring in early childhood, a new study suggests.

Research looking at the effect of prenatal exposure to cannabis on offspring is growing. It is known to affect childhood cognition and behavior; however, there is little work to date on how it affects metabolic outcomes, said lead author Brianna F. Moore, PhD.

“Officially, the American Academy of Obstetricians and Gynecologists recommends that women do not use cannabis during pregnancy or while breastfeeding to limit the effects on offspring. There’s really a lot we don’t know, but researchers across the country are starting to look into this more, and there are signs that it isn’t great for the offspring,” Dr. Moore, assistant professor at the Colorado School of Public Health in Aurora, said in an interview.

And she noted that while some women turn to cannabis to manage the challenging symptoms of pregnancy, “Clinicians should encourage pregnant women to refrain from using cannabis; it is best for these pregnant women to talk to their physicians about alternative ways of managing these symptoms.”

The findings were published online March 31 in the Journal of Clinical Endocrinology & Metabolism.
 

Study of mother and 5-year-old child pairs

The researchers assessed 103 sets of mothers and children from the Healthy Start study. At 27 weeks of gestation, the investigators assessed 12 metabolites of cannabis/cannabinoids in urine samples. Results from these samples were used to categorize fetal exposure to cannabis as either not exposed or exposed. They found that about 15% of the mothers had traceable amounts of cannabinoids, suggesting fetal cannabis exposure.

At follow-up, the study team assessed fat-free mass and fat mass using air displacement plethysmography among the offspring around age 5. They used generalized linear models to approximate the relationship between fetal exposure to cannabis with metabolic measures such as insulin, glucose, and homeostatic model assessment of insulin resistance (HOMA-IR), and adiposity measures such as body mass index, fat-free mass, fat mass, adiposity, and BMI z-scores.

The findings showed that, compared with nonexposed offspring, exposed offspring had greater:

• Fasting glucose (5.6 mg/dL; 95% confidence interval [CI], 0.8-10.3).
• Fat-free mass (1.2 kg; 95% CI, 0.4-2.0).
• Fat mass (1.0 kg; 95% CI, 0.3-1.7).
• Adiposity (2.6%; 95% CI, 0.1-5.2).

“This finding may suggest that fetal exposure to cannabis contributes to higher fasting glucose levels via a direct effect on the pancreatic β-cells. However, we cannot draw conclusions about β-cell response to glucose because we did not perform oral glucose tolerance tests,” the study authors wrote.

Notably, however, there was no relationship between BMI z-scores, BMI, or HOMA-IR and fasting insulin, the study team found.

Study limitations include the small sample size and lack of self-report data on cannabis use to differentiate between direct use and exposure to cannabis, Dr. Moore acknowledged.

Given the small sample size, the researchers were unable to look at dose-response, which future studies will focus on, Dr. Moore noted. Future efforts will also focus on comparing the effects of tetrahydrocannabinol (THC) and cannabidiol (CBD), Dr. Moore added.

“This is a relatively new field, so there’s still work to be done. This is just one study, and we need to study this more in other cohorts to confirm our findings,” she concluded.

Dr. Moore has reported no relevant financial relationships.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist was associated with a 37% increase in the relative risk of gallbladder or biliary disease, compared with controls – especially when used at high doses, for a longer time, and for weight loss rather than type 2 diabetes – a new meta-analysis has found.

The results “indicate that physicians and patients should be concerned about the risks of gallbladder or biliary diseases with using GLP-1 agonists,” study authors Liyun He and colleagues from Peking Union Medical College, Beijing, summarize.

However, “the overall absolute risk increase for gallbladder and biliary disease with use of GLP-1 receptor agonists was small (an additional 27 cases per 10,000 persons treated per year),” they note.

“This absolute risk increase should be weighed against the benefits of treatment with GLP-1 agonists,” which include glucose control, decreased cardiovascular risk, and weight loss, they add.

The findings are from a meta-analysis of 76 randomized controlled trials of GLP-1 agonists published online March 28 in JAMA Internal Medicine.

In an accompanying editorial, Shanzay Haider, MD, and Kasia J. Lipska, MD, also characterize the absolute risk of these complications as “modest.”

“The highest risk for these complications,” they add, “occurred among individuals in the weight loss, compared with the type 2 diabetes studies (119 vs. 13 more events per 10,000 persons per year).”

“Ultimately, the decision to start, continue, or change the dose of a GLP-1 agonist should be reached through a collaborative and individualized discussion between a clinician and a patient,” Dr. Haider and Dr. Lipska, from Yale School of Medicine, New Haven, Conn., summarize.

The study authors also note that few of the trials reported biliary-related events.

“Future trials [of drugs in this class] should prespecify gallbladder and biliary diseases as potential adverse events, and fully test for and report on these outcomes,” they urge.   

Certain drugs in this class are now approved by the U.S. Food and Drug Administration for weight loss at higher doses than for type 2 diabetes – subcutaneous liraglutide (3.0 mg) and subcutaneous semaglutide (2.4 mg) – “suggesting that GLP-1 agonist drugs will increasingly be used at high doses for weight control,” the authors note.

Controversial link

The association between GLP-1 agonists and gallbladder or biliary disease is controversial, the authors write.

Several randomized controlled trials reported higher rates of gallbladder disorders in patients who received a GLP-1 agonist versus placebo, but it is not clear if this is a class effect.

Liraglutide “has drawn the most attention” about this risk, and a post-hoc analysis of the LEADER trial found a significantly increased risk of acute biliary obstruction with liraglutide versus placebo.

To investigate this, the researchers identified 76 randomized controlled trials of GLP-1 agonists in 103,371 patients that had data for the following safety outcomes: cholelithiasis (gallstones, 61 trials), cholecystitis (inflamed gallbladder, 53 trials), biliary disease (21 trials), cholecystectomy (surgical removal of the gallbladder, seven trials), and biliary cancer (12 trials).

Sixty trials were for type 2 diabetes, 13 were for weight loss, and three were for nonalcoholic steatohepatitis, polycystic ovary syndrome, and schizophrenia. They were classed as short or long (≤ 26 weeks or > 26 weeks).

The GLP-1 agonists were liraglutide (21 trials), subcutaneous semaglutide (14), dulaglutide (11), exenatide (9), albiglutide (8), oral semaglutide (8), and lixisenatide (6). 

Participants were a mean age of 58 years and 41% were women. They had a mean BMI of 31.6 kg/m² and 36.9 kg/m² in trials of GLP-1 agonists for type 2 diabetes and weight loss, respectively.  

Patients who received a GLP-1 agonist versus controls had significantly increased rates of cholelithiasis (RR, 1.27; P = .001), cholecystitis (RR, 1.36; P < .001), biliary disease (RR, 1.55; P = .02), and cholecystectomy (RR, 1.70; P < .001) but a nonsignificant increased rate of biliary cancer (RR, 1.43; P = .22).

Use of GLP-1 agonists was associated with a greater increased risk of gallbladder or biliary diseases in trials for weight loss (RR, 2.29) than in trials for type 2 diabetes or other diseases (RR, 1.27; P < .001 for interaction).

Use of these drugs was also associated with higher risks of these complications at higher doses and when given for a longer duration.     

Limitations of the meta-analysis include that the individual studies were not designed to evaluate the risk of gallbladder or biliary diseases associated with GLP-1 agonists.

Also, biliary-related events may have been under-reported, because this was not a predefined safety outcome in most of the trials. The meta-analysis lacked patient-level data, and it may have been underpowered for subgroup analyses.       

The work was supported by grants from the National Natural Science Foundation of China, the Beijing Municipal Natural Science Foundation, the Nonprofit Central Research Institute Fund of the Chinese Academy of Medical Sciences, the CAMS Innovation Fund for Medical Sciences, and the Training Program for Excellent Talents in Dongcheng District. The researchers have no relevant financial disclosures.

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

Jessica Furby struggled with weight most of her life, constantly dieting and exercising to shed pounds. But nothing seemed to help. By her 22nd birthday, she tipped the scales at more than 300 pounds.

So, in 2011, while a college student in Pittsburgh, she decided to have gastric band surgery. Doctors placed a synthetic belt around her stomach to limit what she could eat. It seemed like a good option at the time and, after her surgery, she lost about 60 pounds.

But the benefits didn’t last. In the months that followed, she had pain and other complications. Worst of all, she eventually regained all the weight she’d lost – and then some. By 2016, she weighed 350 pounds and was becoming prediabetic.

That’s when she decided to have the band removed and, on her doctor’s recommendation, had gastric sleeve surgery.

Studies have found the sleeve surgeries carry fewer complications and a much higher success rate than gastric band procedures, which Ms. Furby’s experience has confirmed.

Today, at age 32, she’s down to 288 pounds and says she is on her way to hitting her ultimate goal of 200 pounds.

“The surgery has been a godsend,” she said. “I have not had any complications with it at all. The sleeve was life-changing for me.”

Ms. Furby’s experience has become more common as the risks, complications, and failures of gastric band surgeries have been rising over the past decade.

More band patients are choosing to have conversion surgery to gastric sleeve and gastric bypass. At the same time, fewer doctors are doing gastric band procedures, because of problems like Ms. Furby’s.

According to the latest figures from the American Society for Metabolic and Bariatric Surgery, gastric band procedures account for fewer than 1% of the 256,000 bariatric operations done in the United States each year, while gastric sleeves add up to nearly 60%. That makes sleeve surgeries the most commonly performed bariatric operation today.

By comparison, 35% of bariatric surgeries were gastric band procedures in 2011, while sleeve operations accounted for under 18%.

Ms. Furby’s surgeon, Anita P. Courcoulas, MD, said the trend is being driven by many of the things Ms.Furby experienced firsthand.

Dr. Courcoulas, chief of minimally invasive bariatric and general surgery at the University of Pittsburgh, said there are two main reasons for the decline in gastric band procedures.

“It has been shown to be less effective for weight loss [than] other bariatric surgical procedures, and band intolerance often results in band removal,” she noted.

Gastric sleeve, followed by gastric bypass, are the two most commonly performed operations in the United States and worldwide, she said.

Dr. Courcoulas said the shift from gastric bypass to gastric sleeve procedures “is likely driven by the decline in the band usage, patient preferences for a less invasive operation, such as the sleeve compared to bypass, and surgeon preferences about which operation(s) to offer a given patient.”

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, agrees that gastric band complications and failures, in addition to ineffective weight loss, are behind the trend, driving patients and doctors to choose safer and more effective procedures.

He said the Cleveland Clinic no longer does band operations, and he has done a lot of conversions.

“Around 50%-60% of [gastric band] patients require reoperation to take care of the complications,” he says. “So, when you have a surgery where more than half of the time the patients require reoperation, we cannot claim that’s a safe operation.”
 

Evolution in bariatric surgery

Bariatric surgeries for weight loss date back to the 1950s and 1960s, when surgeons at the University of Minnesota first did experimental bypass operations. Adjustable gastric banding appeared in the late 1970s and early 1980s.

But these procedures didn’t gain widespread mainstream use until gastric band procedures gained full Food and Drug Administration approval in 2001. Clinical trials have found people who have bariatric surgery have a significantly lower risk of heart disease and other obesity-related health problems.

In the decade that followed the FDA’s approval of gastric band surgery, it became a popular weight loss procedure, accounting for more than a third of all bariatric surgeries by 2011.

“Fifteen to 20 years ago, [gastric] band was the most commonly performed procedure for bariatric surgery worldwide and in the United States,” Dr. Aminian said. “It was very easy to do, it was quick – it takes 20 minutes to do the procedure – recovery was short, and initially patients had great outcomes. They would lose weight and were healthy.”

But over the past decade, surgeons found that patients often regained the weight they’d lost, and complication and failure rates rose.

“Because the [gastric] band is a foreign body that we place inside the body, many patients had complications related to that foreign body,” Dr. Aminian said.

The band can sometimes move or be displaced, causing blockage of the stomach, experts noted. Other common complications include nausea, vomiting, acid reflux, and esophageal issues (such as a hard time swallowing). Some patients feel pain, constant food cravings, or that they can’t eat or drink anything. And painful infections and other problems can develop with the tubing or the port placed under the skin that is connected to the band, which doctors use to make adjustments after surgery.

“Scar tissue can also form around the [gastric] band that can cause a blockage in the stomach,” Dr. Aminian said. “Then if the band is too tight, it can erode into the stomach tissue or even go inside the stomach and cause perforation or bleeding.”

By contrast, gastric sleeve and bypass procedures have been found to be safer, result in longer-lasting weight loss, carry fewer complications, and require fewer patient reoperations. Dr. Aminian estimates that 2%-3% of patients need second operations.

Another key factor: Metabolic ‘reset’

Sleeve and bypass procedures offer another critical advantage over band operations: They help reset the body’s metabolism better, changing appetite- and weight-related hormones in the body.

Those hormones can affect food cravings, help people feel full after eating, or boost weight gain in ways that can trump willpower, experts say.

“The [gastric] band doesn’t change the hormones in the body, it’s just a restrictive band around the esophagus or the upper part of the stomach, so it limits the patient’s ability to eat too much,” Dr. Aminian said. “That’s why it doesn’t have the metabolic effects.”

But other procedures, like the gastric sleeve, change the hormones in the body. Removing the source of those hormones means the patient won’t have the same appetite, Dr. Aminian said.

“And that’s why it’s very effective. The problem with the [gastric] band is the patient always has the feeling and desire to eat – they’re always hungry. That’s why in the long run, they fail,” he said.

“They change the setpoints,” Dr. Aminian said. “When the hormones in your body change, the [metabolic] setpoint in the brain also changes.”

He likens the metabolic setpoint to a thermostat in your home that regulates temperature inside.

“When a patient goes on a diet or goes on the [gastric] band, the thermostat doesn’t change,” he says. “They may lose some weight, but they’re going to regain it because the thermostat is the same. But when the hormones in your body change, then the thermostat will change and you’re not going to regain the weight that you have lost.”

Sachin Kukreja, MD, a surgeon and CEO at DFW Bariatrics and General Surgery in Dallas, said he believes these metabolic changes are the biggest things behind successful surgeries.

“People synonymize bariatric surgery with weight loss surgery, but really the metrics we should be using are more related to metabolic measures,” said Dr. Kukreja, who hasn’t done a band surgery since 2013. “And so, the metabolic parameters that change with bariatric surgery are much more significant in the setting with sleeve and gastric sleeve, and much less significant with [gastric] band.”

David Arterburn, MD, agrees that resetting metabolism is important but said the issue is “controversial and challenging” among bariatric surgeons.

“The metabolic setpoint is the idea that we have a biologically controlled set body weight that we will always return to. Clearly, this is not the case for everyone, as some people lose and maintain long-term weight loss,” said Dr. Arterburn, a general internist and bariatric surgery researcher at Kaiser Permanente Washington Health Research Institute in Seattle.
 

Postop lifestyle changes critical to success

Bariatric surgeons and patients alike also say that no surgical procedure is a magic-bullet solution for weight loss. Patients who have any type of bariatric surgery must embrace postop lifestyle changes – adopting healthier diets, getting more exercise, cutting out unhealthy habits – to lose weight and maintain weight loss.

Jan Lasecki, 54, a health care specialist in Akron, Ohio, who had band-to-sleeve conversion surgery in 2020, said the postop follow-up was at least as important as the surgery itself in helping her shed pounds.

She said at first, she chose gastric band surgery several years ago because it was “less invasive” than gastric sleeve or bypass. But while she lost about 50 pounds, she regained it after about 6 years and had other complications.

So, 2 years ago, Ms. Lasecki had two surgeries 6 months apart – one to remove her band, and a second to create a gastric sleeve. And the results, she said, have been very successful, in part because of the changes she made after surgery, with the help of her doctor’s staff.

“I have now lost about 90 pounds and have kept if off since surgery,” she says. “I would tell anyone considering any bariatric surgery, it was definitely worth it [and] having the sleeve resulted in greater weight loss.”

The follow-up was key to the success, she said.

The staff “have the tools and support to help you when you tend to fall back on old behaviors and start to regain weight,” Ms. Lasecki said. “They can help you before it gets out of control. I had no issues following either procedure from a surgery perspective.”

Sally and Robert Cordova – who had gastric bypass and sleeve surgeries, respectively, 3 years ago – agreed that the postop lifestyle changes are critical to success.

“When we agreed to have this surgery, we agreed that this will be a lifestyle change for the rest of our lives,” said Sally, 48, an accounting specialist who’s lost 150 pounds – half her body weight – since her surgery. “You can’t just get to your ideal weight and then stop.”

Robert, 47, a federal border control agent whose workmates nicknamed him “Big Rob” when he tipped the scales at 336 pounds, said it’s a mistake to think of the surgery as a “magic-bullet” solution to obesity. There’s more to it than that, he said.

“One of the things I like about the process I’ve taken is, in my opinion, they set you up for success,” he said. “Because it’s not just having the surgery and you’re done; it’s all the classes educating you about all the lifestyle changes you have to do, and starting them before the surgery. The only people that I know personally who haven’t been successful with the surgery are those who haven’t made the lifestyle changes.”

Today, at 230 pounds, Robert says he’s never felt better.

“I feel great,” he says. “I have become more active, obviously doing everything is a lot easier. It got to the point where it was a task to just tying up my shoes!”
 

Should band patients convert to sleeve or bypass?

Bariatric surgeons interviewed for this article were reluctant to say that all people who had gastric band procedures should convert to gastric sleeve or bypass. But they made it clear that sleeve and bypass procedures are safer and more effective than gastric band surgery, which is why it is rarely done today.

“If a patient experiences poor weight loss or complications from a band, they can consider conversion/revision to a sleeve or bypass,” said Dr. Courcoulas, echoing the views of other doctors.

“The choice of revision procedure should be based on patient factors, including diabetes and total weight. Converting a band to a sleeve is a technically easier operation, and some studies show that there are fewer complications, compared to conversion to a bypass. These considerations need to be balanced with data that show that both weight loss and metabolic improvements such as diabetes are greater after bypass, compared to sleeve.”

Doctors and experts also say it’s important for patients who are considering a gastric band conversion to gastric sleeve or bypass to understand the differences among these three primary procedures, all endorsed by the American Society for Metabolic and Bariatric Surgery.

Here’s a primer, including the pros and cons of each procedure:
 

Gastric band

In gastric band surgery, an adjustable gastric band made of silicone is placed around the top part of the stomach, creating a small pouch above it, to limit the amount of food a person can eat. The size of the opening between the pouch and the stomach can be adjusted with fluid injections through a port placed underneath the skin.

Food goes through the stomach but is limited by the smaller opening of the band.

Advantages:

• Lowest rate of complications right after surgery.
• No division of the stomach or intestines.
• Patients go home on the day of surgery, and recovery is quick.
• The band can be removed, if necessary.

Disadvantages:

• The band may need to be adjusted from time to time, and patients must make monthly office visits during the first year.
• There’s less weight loss than with other surgical procedures.
• It comes with the risk of band movement (slippage) or damage to the stomach over time (erosion).
• The surgery means that a foreign implant has to remain in the body.
• It has a high rate of reoperation.
• The surgery can bring swallowing problems, enlargement of the esophagus, and other complications.

Gastric sleeve

For laparoscopic sleeve gastrectomy – often called gastric sleeve – surgeons remove about 80% of the stomach, so the remaining stomach is the size and shape of a banana.

The new, smaller stomach holds less food and liquid, reducing how much food (and how many calories) the patient can get. By removing the portion of the stomach that produces hunger and appetite hormones, the surgery also helps reset the body’s metabolism – decreasing hunger, increasing feelings of fullness, and allowing the body to reach and maintain a healthy weight as well as control blood sugar.

Advantages:

• It’s technically simple and has a short surgery time.
• It can be done in certain patients with high-risk medical conditions.
• It may be the first step for patients with severe obesity or as a bridge to gastric bypass.
• The surgery brings effective weight loss and improvement of obesity-related conditions (typically 50%-60%, by Mayo Clinic estimates), with a low complication rate (2%-3%).

Disadvantages:

• Nonreversible procedure.
• May worsen or cause new reflux and heartburn.
• Less impact on metabolism, compared to bypass procedures.

Gastric bypass

Gastric bypass, also known as the Roux-en-Y gastric bypass (French for “in the form of a Y”) is another effective procedure used to treat obesity and obesity-related diseases (done laparoscopically since the 1990s).

For the operation, surgeons divide the stomach into a smaller top portion (pouch) about the size of an egg, then the larger part of the stomach is bypassed and no longer stores or digests food.

The small intestine is divided and connected to the new egg-sized stomach pouch to allow food to pass.

Gastric bypass works by limiting the amount of food and calories a patient can consume. It also decreases hunger and increases fullness, allowing the patient to reach and maintain a healthy weight. The impact on hormones and metabolic health often results in improvement of diabetes and helps patients with reflux.

Advantages:

• Reliable and long-lasting weight loss.
• Effective for remission of obesity-associated conditions.
• Effective weight loss (60%-70%, by Mayo Clinic estimates).

Disadvantages:

• Technically more complex when compared to gastric sleeve or band.
• More vitamin and mineral deficiencies than with gastric sleeve or band.
• Risk for small bowel complications and obstruction, as well as ulcers, especially with NSAID or tobacco use.
• May cause “dumping syndrome,” a feeling of sickness after eating or drinking, especially sweets.

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

Editor’s Note: This story has been updated to properly identify a product referenced in the story.

Jessica Furby struggled with weight most of her life, constantly dieting and exercising to shed pounds. But nothing seemed to help. By her 22nd birthday, she tipped the scales at more than 300 pounds.

So, in 2011, while a college student in Pittsburgh, she decided to have gastric band surgery. Doctors placed a synthetic belt around her stomach to limit what she could eat. It seemed like a good option at the time and, after her surgery, she lost about 60 pounds.

But the benefits didn’t last. In the months that followed, she had pain and other complications. Worst of all, she eventually regained all the weight she’d lost – and then some. By 2016, she weighed 350 pounds and was becoming prediabetic.

That’s when she decided to have the band removed and, on her doctor’s recommendation, had gastric sleeve surgery.

Studies have found the sleeve surgeries carry fewer complications and a much higher success rate than gastric band procedures, which Ms. Furby’s experience has confirmed.

Today, at age 32, she’s down to 288 pounds and says she is on her way to hitting her ultimate goal of 200 pounds.

“The surgery has been a godsend,” she said. “I have not had any complications with it at all. The sleeve was life-changing for me.”

Ms. Furby’s experience has become more common as the risks, complications, and failures of gastric band surgeries have been rising over the past decade.

More band patients are choosing to have conversion surgery to gastric sleeve and gastric bypass. At the same time, fewer doctors are doing gastric band procedures, because of problems like Ms. Furby’s.

According to the latest figures from the American Society for Metabolic and Bariatric Surgery, gastric band procedures account for fewer than 1% of the 256,000 bariatric operations done in the United States each year, while gastric sleeves add up to nearly 60%. That makes sleeve surgeries the most commonly performed bariatric operation today.

By comparison, 35% of bariatric surgeries were gastric band procedures in 2011, while sleeve operations accounted for under 18%.

Ms. Furby’s surgeon, Anita P. Courcoulas, MD, said the trend is being driven by many of the things Ms.Furby experienced firsthand.

Dr. Courcoulas, chief of minimally invasive bariatric and general surgery at the University of Pittsburgh, said there are two main reasons for the decline in gastric band procedures.

“It has been shown to be less effective for weight loss [than] other bariatric surgical procedures, and band intolerance often results in band removal,” she noted.

Gastric sleeve, followed by gastric bypass, are the two most commonly performed operations in the United States and worldwide, she said.

Dr. Courcoulas said the shift from gastric bypass to gastric sleeve procedures “is likely driven by the decline in the band usage, patient preferences for a less invasive operation, such as the sleeve compared to bypass, and surgeon preferences about which operation(s) to offer a given patient.”

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, agrees that gastric band complications and failures, in addition to ineffective weight loss, are behind the trend, driving patients and doctors to choose safer and more effective procedures.

He said the Cleveland Clinic no longer does band operations, and he has done a lot of conversions.

“Around 50%-60% of [gastric band] patients require reoperation to take care of the complications,” he says. “So, when you have a surgery where more than half of the time the patients require reoperation, we cannot claim that’s a safe operation.”
 

Evolution in bariatric surgery

Bariatric surgeries for weight loss date back to the 1950s and 1960s, when surgeons at the University of Minnesota first did experimental bypass operations. Adjustable gastric banding appeared in the late 1970s and early 1980s.

But these procedures didn’t gain widespread mainstream use until gastric band procedures gained full Food and Drug Administration approval in 2001. Clinical trials have found people who have bariatric surgery have a significantly lower risk of heart disease and other obesity-related health problems.

In the decade that followed the FDA’s approval of gastric band surgery, it became a popular weight loss procedure, accounting for more than a third of all bariatric surgeries by 2011.

“Fifteen to 20 years ago, [gastric] band was the most commonly performed procedure for bariatric surgery worldwide and in the United States,” Dr. Aminian said. “It was very easy to do, it was quick – it takes 20 minutes to do the procedure – recovery was short, and initially patients had great outcomes. They would lose weight and were healthy.”

But over the past decade, surgeons found that patients often regained the weight they’d lost, and complication and failure rates rose.

“Because the [gastric] band is a foreign body that we place inside the body, many patients had complications related to that foreign body,” Dr. Aminian said.

The band can sometimes move or be displaced, causing blockage of the stomach, experts noted. Other common complications include nausea, vomiting, acid reflux, and esophageal issues (such as a hard time swallowing). Some patients feel pain, constant food cravings, or that they can’t eat or drink anything. And painful infections and other problems can develop with the tubing or the port placed under the skin that is connected to the band, which doctors use to make adjustments after surgery.

“Scar tissue can also form around the [gastric] band that can cause a blockage in the stomach,” Dr. Aminian said. “Then if the band is too tight, it can erode into the stomach tissue or even go inside the stomach and cause perforation or bleeding.”

By contrast, gastric sleeve and bypass procedures have been found to be safer, result in longer-lasting weight loss, carry fewer complications, and require fewer patient reoperations. Dr. Aminian estimates that 2%-3% of patients need second operations.

Another key factor: Metabolic ‘reset’

Sleeve and bypass procedures offer another critical advantage over band operations: They help reset the body’s metabolism better, changing appetite- and weight-related hormones in the body.

Those hormones can affect food cravings, help people feel full after eating, or boost weight gain in ways that can trump willpower, experts say.

“The [gastric] band doesn’t change the hormones in the body, it’s just a restrictive band around the esophagus or the upper part of the stomach, so it limits the patient’s ability to eat too much,” Dr. Aminian said. “That’s why it doesn’t have the metabolic effects.”

But other procedures, like the gastric sleeve, change the hormones in the body. Removing the source of those hormones means the patient won’t have the same appetite, Dr. Aminian said.

“And that’s why it’s very effective. The problem with the [gastric] band is the patient always has the feeling and desire to eat – they’re always hungry. That’s why in the long run, they fail,” he said.

“They change the setpoints,” Dr. Aminian said. “When the hormones in your body change, the [metabolic] setpoint in the brain also changes.”

He likens the metabolic setpoint to a thermostat in your home that regulates temperature inside.

“When a patient goes on a diet or goes on the [gastric] band, the thermostat doesn’t change,” he says. “They may lose some weight, but they’re going to regain it because the thermostat is the same. But when the hormones in your body change, then the thermostat will change and you’re not going to regain the weight that you have lost.”

Sachin Kukreja, MD, a surgeon and CEO at DFW Bariatrics and General Surgery in Dallas, said he believes these metabolic changes are the biggest things behind successful surgeries.

“People synonymize bariatric surgery with weight loss surgery, but really the metrics we should be using are more related to metabolic measures,” said Dr. Kukreja, who hasn’t done a band surgery since 2013. “And so, the metabolic parameters that change with bariatric surgery are much more significant in the setting with sleeve and gastric sleeve, and much less significant with [gastric] band.”

David Arterburn, MD, agrees that resetting metabolism is important but said the issue is “controversial and challenging” among bariatric surgeons.

“The metabolic setpoint is the idea that we have a biologically controlled set body weight that we will always return to. Clearly, this is not the case for everyone, as some people lose and maintain long-term weight loss,” said Dr. Arterburn, a general internist and bariatric surgery researcher at Kaiser Permanente Washington Health Research Institute in Seattle.
 

Postop lifestyle changes critical to success

Bariatric surgeons and patients alike also say that no surgical procedure is a magic-bullet solution for weight loss. Patients who have any type of bariatric surgery must embrace postop lifestyle changes – adopting healthier diets, getting more exercise, cutting out unhealthy habits – to lose weight and maintain weight loss.

Jan Lasecki, 54, a health care specialist in Akron, Ohio, who had band-to-sleeve conversion surgery in 2020, said the postop follow-up was at least as important as the surgery itself in helping her shed pounds.

She said at first, she chose gastric band surgery several years ago because it was “less invasive” than gastric sleeve or bypass. But while she lost about 50 pounds, she regained it after about 6 years and had other complications.

So, 2 years ago, Ms. Lasecki had two surgeries 6 months apart – one to remove her band, and a second to create a gastric sleeve. And the results, she said, have been very successful, in part because of the changes she made after surgery, with the help of her doctor’s staff.

“I have now lost about 90 pounds and have kept if off since surgery,” she says. “I would tell anyone considering any bariatric surgery, it was definitely worth it [and] having the sleeve resulted in greater weight loss.”

The follow-up was key to the success, she said.

The staff “have the tools and support to help you when you tend to fall back on old behaviors and start to regain weight,” Ms. Lasecki said. “They can help you before it gets out of control. I had no issues following either procedure from a surgery perspective.”

Sally and Robert Cordova – who had gastric bypass and sleeve surgeries, respectively, 3 years ago – agreed that the postop lifestyle changes are critical to success.

“When we agreed to have this surgery, we agreed that this will be a lifestyle change for the rest of our lives,” said Sally, 48, an accounting specialist who’s lost 150 pounds – half her body weight – since her surgery. “You can’t just get to your ideal weight and then stop.”

Robert, 47, a federal border control agent whose workmates nicknamed him “Big Rob” when he tipped the scales at 336 pounds, said it’s a mistake to think of the surgery as a “magic-bullet” solution to obesity. There’s more to it than that, he said.

“One of the things I like about the process I’ve taken is, in my opinion, they set you up for success,” he said. “Because it’s not just having the surgery and you’re done; it’s all the classes educating you about all the lifestyle changes you have to do, and starting them before the surgery. The only people that I know personally who haven’t been successful with the surgery are those who haven’t made the lifestyle changes.”

Today, at 230 pounds, Robert says he’s never felt better.

“I feel great,” he says. “I have become more active, obviously doing everything is a lot easier. It got to the point where it was a task to just tying up my shoes!”
 

Should band patients convert to sleeve or bypass?

Bariatric surgeons interviewed for this article were reluctant to say that all people who had gastric band procedures should convert to gastric sleeve or bypass. But they made it clear that sleeve and bypass procedures are safer and more effective than gastric band surgery, which is why it is rarely done today.

“If a patient experiences poor weight loss or complications from a band, they can consider conversion/revision to a sleeve or bypass,” said Dr. Courcoulas, echoing the views of other doctors.

“The choice of revision procedure should be based on patient factors, including diabetes and total weight. Converting a band to a sleeve is a technically easier operation, and some studies show that there are fewer complications, compared to conversion to a bypass. These considerations need to be balanced with data that show that both weight loss and metabolic improvements such as diabetes are greater after bypass, compared to sleeve.”

Doctors and experts also say it’s important for patients who are considering a gastric band conversion to gastric sleeve or bypass to understand the differences among these three primary procedures, all endorsed by the American Society for Metabolic and Bariatric Surgery.

Here’s a primer, including the pros and cons of each procedure:
 

Gastric band

In gastric band surgery, an adjustable gastric band made of silicone is placed around the top part of the stomach, creating a small pouch above it, to limit the amount of food a person can eat. The size of the opening between the pouch and the stomach can be adjusted with fluid injections through a port placed underneath the skin.

Food goes through the stomach but is limited by the smaller opening of the band.

Advantages:

• Lowest rate of complications right after surgery.
• No division of the stomach or intestines.
• Patients go home on the day of surgery, and recovery is quick.
• The band can be removed, if necessary.

Disadvantages:

• The band may need to be adjusted from time to time, and patients must make monthly office visits during the first year.
• There’s less weight loss than with other surgical procedures.
• It comes with the risk of band movement (slippage) or damage to the stomach over time (erosion).
• The surgery means that a foreign implant has to remain in the body.
• It has a high rate of reoperation.
• The surgery can bring swallowing problems, enlargement of the esophagus, and other complications.

Gastric sleeve

For laparoscopic sleeve gastrectomy – often called gastric sleeve – surgeons remove about 80% of the stomach, so the remaining stomach is the size and shape of a banana.

The new, smaller stomach holds less food and liquid, reducing how much food (and how many calories) the patient can get. By removing the portion of the stomach that produces hunger and appetite hormones, the surgery also helps reset the body’s metabolism – decreasing hunger, increasing feelings of fullness, and allowing the body to reach and maintain a healthy weight as well as control blood sugar.

Advantages:

• It’s technically simple and has a short surgery time.
• It can be done in certain patients with high-risk medical conditions.
• It may be the first step for patients with severe obesity or as a bridge to gastric bypass.
• The surgery brings effective weight loss and improvement of obesity-related conditions (typically 50%-60%, by Mayo Clinic estimates), with a low complication rate (2%-3%).

Disadvantages:

• Nonreversible procedure.
• May worsen or cause new reflux and heartburn.
• Less impact on metabolism, compared to bypass procedures.

Gastric bypass

Gastric bypass, also known as the Roux-en-Y gastric bypass (French for “in the form of a Y”) is another effective procedure used to treat obesity and obesity-related diseases (done laparoscopically since the 1990s).

For the operation, surgeons divide the stomach into a smaller top portion (pouch) about the size of an egg, then the larger part of the stomach is bypassed and no longer stores or digests food.

The small intestine is divided and connected to the new egg-sized stomach pouch to allow food to pass.

Gastric bypass works by limiting the amount of food and calories a patient can consume. It also decreases hunger and increases fullness, allowing the patient to reach and maintain a healthy weight. The impact on hormones and metabolic health often results in improvement of diabetes and helps patients with reflux.

Advantages:

• Reliable and long-lasting weight loss.
• Effective for remission of obesity-associated conditions.
• Effective weight loss (60%-70%, by Mayo Clinic estimates).

Disadvantages:

• Technically more complex when compared to gastric sleeve or band.
• More vitamin and mineral deficiencies than with gastric sleeve or band.
• Risk for small bowel complications and obstruction, as well as ulcers, especially with NSAID or tobacco use.
• May cause “dumping syndrome,” a feeling of sickness after eating or drinking, especially sweets.

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

Editor’s Note: This story has been updated to properly identify a product referenced in the story.

Jessica Furby struggled with weight most of her life, constantly dieting and exercising to shed pounds. But nothing seemed to help. By her 22nd birthday, she tipped the scales at more than 300 pounds.

So, in 2011, while a college student in Pittsburgh, she decided to have gastric band surgery. Doctors placed a synthetic belt around her stomach to limit what she could eat. It seemed like a good option at the time and, after her surgery, she lost about 60 pounds.

But the benefits didn’t last. In the months that followed, she had pain and other complications. Worst of all, she eventually regained all the weight she’d lost – and then some. By 2016, she weighed 350 pounds and was becoming prediabetic.

That’s when she decided to have the band removed and, on her doctor’s recommendation, had gastric sleeve surgery.

Studies have found the sleeve surgeries carry fewer complications and a much higher success rate than gastric band procedures, which Ms. Furby’s experience has confirmed.

Today, at age 32, she’s down to 288 pounds and says she is on her way to hitting her ultimate goal of 200 pounds.

“The surgery has been a godsend,” she said. “I have not had any complications with it at all. The sleeve was life-changing for me.”

Ms. Furby’s experience has become more common as the risks, complications, and failures of gastric band surgeries have been rising over the past decade.

More band patients are choosing to have conversion surgery to gastric sleeve and gastric bypass. At the same time, fewer doctors are doing gastric band procedures, because of problems like Ms. Furby’s.

According to the latest figures from the American Society for Metabolic and Bariatric Surgery, gastric band procedures account for fewer than 1% of the 256,000 bariatric operations done in the United States each year, while gastric sleeves add up to nearly 60%. That makes sleeve surgeries the most commonly performed bariatric operation today.

By comparison, 35% of bariatric surgeries were gastric band procedures in 2011, while sleeve operations accounted for under 18%.

Ms. Furby’s surgeon, Anita P. Courcoulas, MD, said the trend is being driven by many of the things Ms.Furby experienced firsthand.

Dr. Courcoulas, chief of minimally invasive bariatric and general surgery at the University of Pittsburgh, said there are two main reasons for the decline in gastric band procedures.

“It has been shown to be less effective for weight loss [than] other bariatric surgical procedures, and band intolerance often results in band removal,” she noted.

Gastric sleeve, followed by gastric bypass, are the two most commonly performed operations in the United States and worldwide, she said.

Dr. Courcoulas said the shift from gastric bypass to gastric sleeve procedures “is likely driven by the decline in the band usage, patient preferences for a less invasive operation, such as the sleeve compared to bypass, and surgeon preferences about which operation(s) to offer a given patient.”

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, agrees that gastric band complications and failures, in addition to ineffective weight loss, are behind the trend, driving patients and doctors to choose safer and more effective procedures.

He said the Cleveland Clinic no longer does band operations, and he has done a lot of conversions.

“Around 50%-60% of [gastric band] patients require reoperation to take care of the complications,” he says. “So, when you have a surgery where more than half of the time the patients require reoperation, we cannot claim that’s a safe operation.”
 

Evolution in bariatric surgery

Bariatric surgeries for weight loss date back to the 1950s and 1960s, when surgeons at the University of Minnesota first did experimental bypass operations. Adjustable gastric banding appeared in the late 1970s and early 1980s.

But these procedures didn’t gain widespread mainstream use until gastric band procedures gained full Food and Drug Administration approval in 2001. Clinical trials have found people who have bariatric surgery have a significantly lower risk of heart disease and other obesity-related health problems.

In the decade that followed the FDA’s approval of gastric band surgery, it became a popular weight loss procedure, accounting for more than a third of all bariatric surgeries by 2011.

“Fifteen to 20 years ago, [gastric] band was the most commonly performed procedure for bariatric surgery worldwide and in the United States,” Dr. Aminian said. “It was very easy to do, it was quick – it takes 20 minutes to do the procedure – recovery was short, and initially patients had great outcomes. They would lose weight and were healthy.”

But over the past decade, surgeons found that patients often regained the weight they’d lost, and complication and failure rates rose.

“Because the [gastric] band is a foreign body that we place inside the body, many patients had complications related to that foreign body,” Dr. Aminian said.

The band can sometimes move or be displaced, causing blockage of the stomach, experts noted. Other common complications include nausea, vomiting, acid reflux, and esophageal issues (such as a hard time swallowing). Some patients feel pain, constant food cravings, or that they can’t eat or drink anything. And painful infections and other problems can develop with the tubing or the port placed under the skin that is connected to the band, which doctors use to make adjustments after surgery.

“Scar tissue can also form around the [gastric] band that can cause a blockage in the stomach,” Dr. Aminian said. “Then if the band is too tight, it can erode into the stomach tissue or even go inside the stomach and cause perforation or bleeding.”

By contrast, gastric sleeve and bypass procedures have been found to be safer, result in longer-lasting weight loss, carry fewer complications, and require fewer patient reoperations. Dr. Aminian estimates that 2%-3% of patients need second operations.

Another key factor: Metabolic ‘reset’

Sleeve and bypass procedures offer another critical advantage over band operations: They help reset the body’s metabolism better, changing appetite- and weight-related hormones in the body.

Those hormones can affect food cravings, help people feel full after eating, or boost weight gain in ways that can trump willpower, experts say.

“The [gastric] band doesn’t change the hormones in the body, it’s just a restrictive band around the esophagus or the upper part of the stomach, so it limits the patient’s ability to eat too much,” Dr. Aminian said. “That’s why it doesn’t have the metabolic effects.”

But other procedures, like the gastric sleeve, change the hormones in the body. Removing the source of those hormones means the patient won’t have the same appetite, Dr. Aminian said.

“And that’s why it’s very effective. The problem with the [gastric] band is the patient always has the feeling and desire to eat – they’re always hungry. That’s why in the long run, they fail,” he said.

“They change the setpoints,” Dr. Aminian said. “When the hormones in your body change, the [metabolic] setpoint in the brain also changes.”

He likens the metabolic setpoint to a thermostat in your home that regulates temperature inside.

“When a patient goes on a diet or goes on the [gastric] band, the thermostat doesn’t change,” he says. “They may lose some weight, but they’re going to regain it because the thermostat is the same. But when the hormones in your body change, then the thermostat will change and you’re not going to regain the weight that you have lost.”

Sachin Kukreja, MD, a surgeon and CEO at DFW Bariatrics and General Surgery in Dallas, said he believes these metabolic changes are the biggest things behind successful surgeries.

“People synonymize bariatric surgery with weight loss surgery, but really the metrics we should be using are more related to metabolic measures,” said Dr. Kukreja, who hasn’t done a band surgery since 2013. “And so, the metabolic parameters that change with bariatric surgery are much more significant in the setting with sleeve and gastric sleeve, and much less significant with [gastric] band.”

David Arterburn, MD, agrees that resetting metabolism is important but said the issue is “controversial and challenging” among bariatric surgeons.

“The metabolic setpoint is the idea that we have a biologically controlled set body weight that we will always return to. Clearly, this is not the case for everyone, as some people lose and maintain long-term weight loss,” said Dr. Arterburn, a general internist and bariatric surgery researcher at Kaiser Permanente Washington Health Research Institute in Seattle.
 

Postop lifestyle changes critical to success

Bariatric surgeons and patients alike also say that no surgical procedure is a magic-bullet solution for weight loss. Patients who have any type of bariatric surgery must embrace postop lifestyle changes – adopting healthier diets, getting more exercise, cutting out unhealthy habits – to lose weight and maintain weight loss.

Jan Lasecki, 54, a health care specialist in Akron, Ohio, who had band-to-sleeve conversion surgery in 2020, said the postop follow-up was at least as important as the surgery itself in helping her shed pounds.

She said at first, she chose gastric band surgery several years ago because it was “less invasive” than gastric sleeve or bypass. But while she lost about 50 pounds, she regained it after about 6 years and had other complications.

So, 2 years ago, Ms. Lasecki had two surgeries 6 months apart – one to remove her band, and a second to create a gastric sleeve. And the results, she said, have been very successful, in part because of the changes she made after surgery, with the help of her doctor’s staff.

“I have now lost about 90 pounds and have kept if off since surgery,” she says. “I would tell anyone considering any bariatric surgery, it was definitely worth it [and] having the sleeve resulted in greater weight loss.”

The follow-up was key to the success, she said.

The staff “have the tools and support to help you when you tend to fall back on old behaviors and start to regain weight,” Ms. Lasecki said. “They can help you before it gets out of control. I had no issues following either procedure from a surgery perspective.”

Sally and Robert Cordova – who had gastric bypass and sleeve surgeries, respectively, 3 years ago – agreed that the postop lifestyle changes are critical to success.

“When we agreed to have this surgery, we agreed that this will be a lifestyle change for the rest of our lives,” said Sally, 48, an accounting specialist who’s lost 150 pounds – half her body weight – since her surgery. “You can’t just get to your ideal weight and then stop.”

Robert, 47, a federal border control agent whose workmates nicknamed him “Big Rob” when he tipped the scales at 336 pounds, said it’s a mistake to think of the surgery as a “magic-bullet” solution to obesity. There’s more to it than that, he said.

“One of the things I like about the process I’ve taken is, in my opinion, they set you up for success,” he said. “Because it’s not just having the surgery and you’re done; it’s all the classes educating you about all the lifestyle changes you have to do, and starting them before the surgery. The only people that I know personally who haven’t been successful with the surgery are those who haven’t made the lifestyle changes.”

Today, at 230 pounds, Robert says he’s never felt better.

“I feel great,” he says. “I have become more active, obviously doing everything is a lot easier. It got to the point where it was a task to just tying up my shoes!”
 

Should band patients convert to sleeve or bypass?

Bariatric surgeons interviewed for this article were reluctant to say that all people who had gastric band procedures should convert to gastric sleeve or bypass. But they made it clear that sleeve and bypass procedures are safer and more effective than gastric band surgery, which is why it is rarely done today.

“If a patient experiences poor weight loss or complications from a band, they can consider conversion/revision to a sleeve or bypass,” said Dr. Courcoulas, echoing the views of other doctors.

“The choice of revision procedure should be based on patient factors, including diabetes and total weight. Converting a band to a sleeve is a technically easier operation, and some studies show that there are fewer complications, compared to conversion to a bypass. These considerations need to be balanced with data that show that both weight loss and metabolic improvements such as diabetes are greater after bypass, compared to sleeve.”

Doctors and experts also say it’s important for patients who are considering a gastric band conversion to gastric sleeve or bypass to understand the differences among these three primary procedures, all endorsed by the American Society for Metabolic and Bariatric Surgery.

Here’s a primer, including the pros and cons of each procedure:
 

Gastric band

In gastric band surgery, an adjustable gastric band made of silicone is placed around the top part of the stomach, creating a small pouch above it, to limit the amount of food a person can eat. The size of the opening between the pouch and the stomach can be adjusted with fluid injections through a port placed underneath the skin.

Food goes through the stomach but is limited by the smaller opening of the band.

Advantages:

• Lowest rate of complications right after surgery.
• No division of the stomach or intestines.
• Patients go home on the day of surgery, and recovery is quick.
• The band can be removed, if necessary.

Disadvantages:

• The band may need to be adjusted from time to time, and patients must make monthly office visits during the first year.
• There’s less weight loss than with other surgical procedures.
• It comes with the risk of band movement (slippage) or damage to the stomach over time (erosion).
• The surgery means that a foreign implant has to remain in the body.
• It has a high rate of reoperation.
• The surgery can bring swallowing problems, enlargement of the esophagus, and other complications.

Gastric sleeve

For laparoscopic sleeve gastrectomy – often called gastric sleeve – surgeons remove about 80% of the stomach, so the remaining stomach is the size and shape of a banana.

The new, smaller stomach holds less food and liquid, reducing how much food (and how many calories) the patient can get. By removing the portion of the stomach that produces hunger and appetite hormones, the surgery also helps reset the body’s metabolism – decreasing hunger, increasing feelings of fullness, and allowing the body to reach and maintain a healthy weight as well as control blood sugar.

Advantages:

• It’s technically simple and has a short surgery time.
• It can be done in certain patients with high-risk medical conditions.
• It may be the first step for patients with severe obesity or as a bridge to gastric bypass.
• The surgery brings effective weight loss and improvement of obesity-related conditions (typically 50%-60%, by Mayo Clinic estimates), with a low complication rate (2%-3%).

Disadvantages:

• Nonreversible procedure.
• May worsen or cause new reflux and heartburn.
• Less impact on metabolism, compared to bypass procedures.

Gastric bypass

Gastric bypass, also known as the Roux-en-Y gastric bypass (French for “in the form of a Y”) is another effective procedure used to treat obesity and obesity-related diseases (done laparoscopically since the 1990s).

For the operation, surgeons divide the stomach into a smaller top portion (pouch) about the size of an egg, then the larger part of the stomach is bypassed and no longer stores or digests food.

The small intestine is divided and connected to the new egg-sized stomach pouch to allow food to pass.

Gastric bypass works by limiting the amount of food and calories a patient can consume. It also decreases hunger and increases fullness, allowing the patient to reach and maintain a healthy weight. The impact on hormones and metabolic health often results in improvement of diabetes and helps patients with reflux.

Advantages:

• Reliable and long-lasting weight loss.
• Effective for remission of obesity-associated conditions.
• Effective weight loss (60%-70%, by Mayo Clinic estimates).

Disadvantages:

• Technically more complex when compared to gastric sleeve or band.
• More vitamin and mineral deficiencies than with gastric sleeve or band.
• Risk for small bowel complications and obstruction, as well as ulcers, especially with NSAID or tobacco use.
• May cause “dumping syndrome,” a feeling of sickness after eating or drinking, especially sweets.

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

Editor’s Note: This story has been updated to properly identify a product referenced in the story.

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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

The U.S. Food and Drug Administration has approved a higher 2-mg dose of the GLP-1 agonist semaglutide (Ozempic, Novo Nordisk) for adults with type 2 diabetes, giving a higher-dose alternative to the previous maximum 1-mg dose of semaglutide, administered by subcutaneous injection once weekly.

Semaglutide is currently available as 0.5-mg and 1-mg doses.

Results from the pivotal SUSTAIN FORTE study of the 2-mg dose (which, like lower-dose semaglutide for type 2 diabetes, comes in a single-use pen injector) showed that when compared head-to-head with a 1-mg/week dose in a 40-week study with 961 randomized patients, the 2-mg regimen led to a significant average incremental reduction in A1c levels of 0.23 percentage points. The 2-mg dose also produced a significant incremental increase in weight loss, with patients losing 0.93 kg more on the higher dose.

The 2-mg dose gives patients with type 2 diabetes and clinicians an “additional option” when a bigger “shift” in blood glucose is needed, said Juan Pablo Frias, MD, National Research Institute, Los Angeles, California, who was lead investigator for SUSTAIN FORTE, in a written statement.

As well as reducing glucose levels, semaglutide has been shown to reduce the risk of major cardiovascular events in adults with type 2 diabetes and known cardiovascular disease.

Semaglutide was approved as a 2.4-mg injectable dose, as Wegovy, in 2021 for weight loss in patients with overweight or obesity.

SUSTAIN FORTE and other trials of semaglutide were sponsored by Novo Nordisk. SURPASS-2 and other trials of tirzepatide were sponsored by Lilly. Dr. Frias was lead investigator for both SUSTAIN FORTE and SURPASS-2, as well as an investigator for other trials sponsored by Lilly, Novo Nordisk, and other companies.

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