Lipid Disorders

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

The metabolically unhealthy obesity phenotype, with its multiple comorbidities, may be the most practical group of people with obesity to screen for Cushing syndrome rather than all patients with obesity.

METHODOLOGY:

• Obesity is a key clinical feature of Cushing syndrome and shares many overlapping characteristics. An ongoing debate continues about the need to screen patients with obesity for the rare endocrine disease, but phenotypes known as metabolically healthy or unhealthy obesity may help better define an at-risk population.
• To assess the prevalence of Cushing syndrome by metabolic health status, researchers conducted a retrospective study of 1008 patients with obesity (mean age, 40 years; 83% women; body mass index ≥ 30) seen at an endocrinology outpatient clinic in Turkey between December 2020 and June 2022.
• They screened patients for Cushing syndrome with an overnight dexamethasone suppression test (1 mg DST), an oral dexamethasone dose given at 11 PM followed by a fasting blood sample for cortisol measurement the next morning. A serum cortisol level < 1.8 mcg/dL indicated normal suppression.
• Patients were categorized into those with metabolically healthy obesity (n = 229) or metabolically unhealthy obesity (n = 779) based on the absence or presence of comorbidities such as diabetes, prediabetes, coronary artery disease, hypertension, or dyslipidemia.

TAKEAWAY:

• The overall prevalence of Cushing syndrome in the study cohort was 0.2%, with only two patients definitively diagnosed after more tests and the remaining 10 classified as having subclinical hypercortisolism.
• Cortisol levels following the 1 mg DST were higher in the metabolically unhealthy obesity group than in the metabolically healthy obesity group (P = .001).
• Among the 12 patients with unsuppressed levels of cortisol, 11 belonged to the metabolically unhealthy obesity group, indicating a strong association between metabolic health and the levels of cortisol.
• The test demonstrated a specificity of 99% and sensitivity of 100% for screening Cushing syndrome in patients with obesity.

IN PRACTICE:

“Screening all patients with obesity for CS [Cushing syndrome] without considering any associated metabolic conditions appears impractical and unnecessary in everyday clinical practice,” the authors wrote. “However, it may be more reasonable and applicable to selectively screen the patients with obesity having comorbidities such as DM [diabetes mellitus], hypertension, dyslipidemia, or coronary artery disease, which lead to a metabolically unhealthy phenotype, rather than all individuals with obesity,” they added.

SOURCE:

The study, led by Sema Hepsen, Ankara Etlik City Hospital, Department of Endocrinology and Metabolism, Ankara, Turkey, was published online in the International Journal of Obesity.

LIMITATIONS:

The single-center design of the study and inclusion of patients from a single racial group may limit the generalizability of the findings. The retrospective design prevented the retrieval of all relevant data on clinical features and fat distribution.

DISCLOSURES:

The study was supported by an open access funding provided by the Scientific and Technological Research Council of Türkiye. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Around one in seven Medicare beneficiaries with a high body mass index (BMI) may be newly eligible for semaglutide treatment after Medicare allowed Part D plans to cover the drug for patients with a BMI ≥ 27 and a history of cardiovascular disease (CVD), regardless of their diabetes status.

METHODOLOGY:

• In March 2024, Medicare approved the coverage of semaglutide by Part D plans for patients with a high BMI and existing CVD, irrespective of their diabetes status. This decision follows the SELECT trial results, showing that semaglutide lowered the risk for cardiovascular events in some patients without diabetes.
• This study aimed to describe the Medicare beneficiaries most likely to be newly eligible for semaglutide treatment and estimated maximum costs to Medicare Part D.
• The researchers included 5111 individuals aged ≥ 65 years with self-reported Medicare enrollment in the National Health and Nutrition Examination Survey between 2011 and 2020, all of whom had a BMI ≥ 27 and were likely to benefit from semaglutide treatment.
• They evaluated the following potential definitions of established CVD that could be considered by the Part D plan: physician-provided diagnosis of myocardial infarction, stroke, coronary artery disease, or angina; a 10-year risk for atherosclerotic CVD between 7.5% and < 20.0%; a 10-year risk for atherosclerotic CVD of ≥ 20%; or fulfillment of any of the previous three criteria.
• Data on interview responses, medication use, clinical examinations, laboratory results, and diabetes diagnoses were obtained from the participants.

TAKEAWAY:

• This study found that 3.6 million individuals (14.2%) were deemed highly likely to qualify for semaglutide treatment for the first time, and broadening the criteria for established CVD could increase this number to 15.2 million individuals (60.9%).
• If all newly eligible beneficiaries were to receive semaglutide treatment, Medicare spending could increase by $34-$145 billion annually.
• Even with more conservative definitions of CVD and a significant portion of individuals not maintaining long-term adherence to semaglutide treatment, costs could still increase by $10 billion annually.
• Younger, generally healthier, female Medicare beneficiaries were still likely to remain ineligible for semaglutide treatment according to the coverage provided by Part D Medicare plans.

IN PRACTICE:

“Although approximately one in seven Medicare beneficiaries with elevated BMI is likely to be newly eligible for semaglutide, the majority will remain ineligible if a narrow definition of established CVD is used by Part D plans. Weight control has benefits for patients with elevated BMI, so the definition of established CVD used by Part D plans for coverage of semaglutide could have outsized public health implications,” the authors wrote.

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women’s Hospital, Boston. It was published online in Annals of Internal Medicine.

LIMITATIONS: 

This analysis relied on self-reported cases of CVD. The study was also limited to only community-dwelling adults. It estimated maximum budgetary impacts but did not account for payment reforms introduced by the Inflation Reduction Act or for absolute contraindications to semaglutide.

DISCLOSURES:

This study did not disclose any sources of funding. Some authors declared receiving grants, serving as consultants, and having other ties with some institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Around one in seven Medicare beneficiaries with a high body mass index (BMI) may be newly eligible for semaglutide treatment after Medicare allowed Part D plans to cover the drug for patients with a BMI ≥ 27 and a history of cardiovascular disease (CVD), regardless of their diabetes status.

METHODOLOGY:

• In March 2024, Medicare approved the coverage of semaglutide by Part D plans for patients with a high BMI and existing CVD, irrespective of their diabetes status. This decision follows the SELECT trial results, showing that semaglutide lowered the risk for cardiovascular events in some patients without diabetes.
• This study aimed to describe the Medicare beneficiaries most likely to be newly eligible for semaglutide treatment and estimated maximum costs to Medicare Part D.
• The researchers included 5111 individuals aged ≥ 65 years with self-reported Medicare enrollment in the National Health and Nutrition Examination Survey between 2011 and 2020, all of whom had a BMI ≥ 27 and were likely to benefit from semaglutide treatment.
• They evaluated the following potential definitions of established CVD that could be considered by the Part D plan: physician-provided diagnosis of myocardial infarction, stroke, coronary artery disease, or angina; a 10-year risk for atherosclerotic CVD between 7.5% and < 20.0%; a 10-year risk for atherosclerotic CVD of ≥ 20%; or fulfillment of any of the previous three criteria.
• Data on interview responses, medication use, clinical examinations, laboratory results, and diabetes diagnoses were obtained from the participants.

TAKEAWAY:

• This study found that 3.6 million individuals (14.2%) were deemed highly likely to qualify for semaglutide treatment for the first time, and broadening the criteria for established CVD could increase this number to 15.2 million individuals (60.9%).
• If all newly eligible beneficiaries were to receive semaglutide treatment, Medicare spending could increase by $34-$145 billion annually.
• Even with more conservative definitions of CVD and a significant portion of individuals not maintaining long-term adherence to semaglutide treatment, costs could still increase by $10 billion annually.
• Younger, generally healthier, female Medicare beneficiaries were still likely to remain ineligible for semaglutide treatment according to the coverage provided by Part D Medicare plans.

IN PRACTICE:

“Although approximately one in seven Medicare beneficiaries with elevated BMI is likely to be newly eligible for semaglutide, the majority will remain ineligible if a narrow definition of established CVD is used by Part D plans. Weight control has benefits for patients with elevated BMI, so the definition of established CVD used by Part D plans for coverage of semaglutide could have outsized public health implications,” the authors wrote.

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women’s Hospital, Boston. It was published online in Annals of Internal Medicine.

LIMITATIONS: 

This analysis relied on self-reported cases of CVD. The study was also limited to only community-dwelling adults. It estimated maximum budgetary impacts but did not account for payment reforms introduced by the Inflation Reduction Act or for absolute contraindications to semaglutide.

DISCLOSURES:

This study did not disclose any sources of funding. Some authors declared receiving grants, serving as consultants, and having other ties with some institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Around one in seven Medicare beneficiaries with a high body mass index (BMI) may be newly eligible for semaglutide treatment after Medicare allowed Part D plans to cover the drug for patients with a BMI ≥ 27 and a history of cardiovascular disease (CVD), regardless of their diabetes status.

METHODOLOGY:

• In March 2024, Medicare approved the coverage of semaglutide by Part D plans for patients with a high BMI and existing CVD, irrespective of their diabetes status. This decision follows the SELECT trial results, showing that semaglutide lowered the risk for cardiovascular events in some patients without diabetes.
• This study aimed to describe the Medicare beneficiaries most likely to be newly eligible for semaglutide treatment and estimated maximum costs to Medicare Part D.
• The researchers included 5111 individuals aged ≥ 65 years with self-reported Medicare enrollment in the National Health and Nutrition Examination Survey between 2011 and 2020, all of whom had a BMI ≥ 27 and were likely to benefit from semaglutide treatment.
• They evaluated the following potential definitions of established CVD that could be considered by the Part D plan: physician-provided diagnosis of myocardial infarction, stroke, coronary artery disease, or angina; a 10-year risk for atherosclerotic CVD between 7.5% and < 20.0%; a 10-year risk for atherosclerotic CVD of ≥ 20%; or fulfillment of any of the previous three criteria.
• Data on interview responses, medication use, clinical examinations, laboratory results, and diabetes diagnoses were obtained from the participants.

TAKEAWAY:

• This study found that 3.6 million individuals (14.2%) were deemed highly likely to qualify for semaglutide treatment for the first time, and broadening the criteria for established CVD could increase this number to 15.2 million individuals (60.9%).
• If all newly eligible beneficiaries were to receive semaglutide treatment, Medicare spending could increase by $34-$145 billion annually.
• Even with more conservative definitions of CVD and a significant portion of individuals not maintaining long-term adherence to semaglutide treatment, costs could still increase by $10 billion annually.
• Younger, generally healthier, female Medicare beneficiaries were still likely to remain ineligible for semaglutide treatment according to the coverage provided by Part D Medicare plans.

IN PRACTICE:

“Although approximately one in seven Medicare beneficiaries with elevated BMI is likely to be newly eligible for semaglutide, the majority will remain ineligible if a narrow definition of established CVD is used by Part D plans. Weight control has benefits for patients with elevated BMI, so the definition of established CVD used by Part D plans for coverage of semaglutide could have outsized public health implications,” the authors wrote.

SOURCE:

The study was led by Alexander Chaitoff, MD, MPH, Center for Healthcare Delivery Sciences, Department of Medicine, Brigham and Women’s Hospital, Boston. It was published online in Annals of Internal Medicine.

LIMITATIONS: 

This analysis relied on self-reported cases of CVD. The study was also limited to only community-dwelling adults. It estimated maximum budgetary impacts but did not account for payment reforms introduced by the Inflation Reduction Act or for absolute contraindications to semaglutide.

DISCLOSURES:

This study did not disclose any sources of funding. Some authors declared receiving grants, serving as consultants, and having other ties with some institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

We know exercise can be a powerful medical intervention. Now scientists are finally starting to understand why.

A recent study in rats found that exercise positively changes virtually every tissue in the body. The research was part of a large National Institutes of Health initiative called MoTrPAC (Molecular Transducers of Physical Activity Consortium) to understand how physical activity improves health and prevents disease. As part of the project, a large human study is also underway.

“What was mind-blowing to me was just how much every organ changed,” said cardiologist Euan A. Ashley, MD, professor of medicine at Stanford University, Stanford, California, and the study’s lead author. “You really are a different person on exercise.”

The study examined hundreds of previously sedentary rats that exercised on a treadmill for 8 weeks. Their tissues were compared with a control group of rats that stayed sedentary.

Your patients, unlike lab animals, can’t be randomly assigned to run on a treadmill until you switch the machine off.

So how do you persuade your patients to become more active?

We asked seven doctors what works for them. They shared 10 of their most effective persuasion tactics.
 

1. Focus on the First Step

“It’s easy to say you want to change behavior,” said Jordan Metzl, MD, a sports medicine specialist at the Hospital for Special Surgery in New York City who instructs medical students on how to prescribe exercise. “It’s much more difficult to do it.”

He compares it with moving a tractor tire from point A to point B. The hardest part is lifting the tire off the ground and starting to move it. “Once it’s rolling, it takes much less effort to keep it going in the same direction,” he said.

How much exercise a patient does is irrelevant until they’ve given that tire its first push.

“Any amount of exercise is better than nothing,” Dr. Ashley said. “Let’s just start with that. Making the move from sitting a lot to standing more has genuine health benefits.” 
 

2. Mind Your Language

Many patients have a deep-rooted aversion to words and phrases associated with physical activity.

“Exercise” is one. “Working out” is another.

“I often tell them they just have to start moving,” said Chris Raynor, MD, an orthopedic surgeon based in Ottawa, Ontario. “Don’t think about it as working out. Think about it as just moving. Start with something they already like doing and work from there.”
 

3. Make It Manageable

This also applies to patients who’re injured and either waiting for or recovering from surgery.

“Joints like motion,” said Rachel M. Frank, MD, an orthopedic surgeon at the University of Colorado Sports Medicine, Denver, Colorado. “The more mobile you can be, the easier your recovery’s going to be.”

That can be a challenge for a patient who wasn’t active before the injury, especially if he or she is fixed on the idea that exercise doesn’t matter unless they do it for 30-45 minutes at a time.

“I try to break it down into manageable bits they can do at home,” Dr. Frank said. “I say, ‘Look, you brush your teeth twice a day, right? Can you do these exercises for 5 or 10 minutes before or after you brush your teeth?’ ”
 

4. Connect Their Interests to Their Activity Level

Chad Waterbury, DPT, thought he knew how to motivate a postsurgical patient to become more active and improve her odds for a full recovery. He told her she’d feel better and have more energy — all the usual selling points.

None of it impressed her.

But one day she mentioned that she’d recently become a grandmother for the first time. Dr. Waterbury, a physical therapist based in Los Angeles, noticed how she lit up when she talked about her new granddaughter.

“So I started giving her scenarios, like taking her daughter to Disneyland when she’s 9 or 10. You have to be somewhat fit to do something like that.”

It worked, and Dr. Waterbury learned a fundamental lesson in motivation. “You have to connect the exercise to something that’s important in their life,” he said.
 

5. Don’t Let a Crisis Go to Waste

“There are very few things more motivating than having a heart attack,” Dr. Ashley said. “For the vast majority of people, that’s a very sobering moment where they reassess everything in their lives.”

There’ll never be a better time to persuade a patient to become more active. In his cardiology practice, Dr. Ashley has seen a lot of patients make that switch.

“They really do start to prioritize their health in a way they never did before,” he said.
 

6. Emphasize the Practical Over the Ideal

Not all patients attach negative feelings to working out. For some, it’s the goal.

Todd Ivan, MD, calls it the “ ’I need to get to the gym’ lament”: Something they’ve aspired to but rarely if ever done.

“I tell them I’d welcome a half-hour walk every day to get started,” said Dr. Ivan, a consultation-liaison psychiatrist at Summa Health in Akron, Ohio. “It’s a way to introduce the idea that fitness begins with small adjustments.”
 

7. Go Beneath the Surface

“Exercise doesn’t generally result in great weight loss,” said endocrinologist Karl Nadolsky, DO, an obesity specialist and co-host of the Docs Who Lift podcast.

But a lot of his patients struggle to break that connection. It’s understandable, given how many times they’ve been told they’d weigh less if they moved more.

Dr. Nadolsky tells them it’s what’s on the inside that counts. “I explain it as very literal, meaning their physical health, metabolic health, and mental health.”

By reframing physical activity with an internal rather than external focus — the plumbing and wiring vs the shutters and shingles — he gives them permission to approach exercise as a health upgrade rather than yet another part of their lifelong struggle to lose weight.

“A significant number of our patients respond well to that,” he said.
 

8. Appeal to Their Intellect

Some patients think like doctors: No matter how reluctant they may be to change their mind about something, they’ll respond to evidence.

Dr. Frank has learned to identify these scientifically inclined patients. “I’ll flood them with data,” she said. “I’ll say, ‘These studies show that if you do x, y, z, your outcome will be better.’ ”

Dr. Ashley takes a similar approach when his patients give him the most common reason for not exercising: “I don’t have time.”

He tells them that exercise doesn’t take time. It gives you time.

That’s according to a 2012 study of more than 650,000 adults that associated physical activity with an increased lifespan.

As one of the authors said in an interview, a middle-aged person who gets 150 minutes a week of moderate exercise will, on average, gain 7 more minutes of life for each minute of exercise, compared with someone who doesn’t get any exercise.

The strategy works because it brings patients out of their day-to-day lives and into the future, Dr. Ashley said.

“What about your entire life?” he asks them. “You’re actually in this world for 80-plus years, you hope. How are you going to spend that? You have to think about that when you’re in your 40s and 50s.”
 

9. Show Them the Money

Illness and injury, on top of everything else, can be really expensive.

Even with good insurance, a health problem that requires surgery and/or hospitalization might cost thousands of dollars out of pocket. With mediocre insurance, it might be tens of thousands.

Sometimes, Dr. Frank said, it helps to remind patients of the price they paid for their treatment. “I’ll say, ‘Let’s get moving so you don’t have to pay for this again.’ ”

Protecting their investment can be a powerful motivation.
 

10. Make It a Team Effort

While the doctors we interviewed have a wide range of specialties — cardiology, sports medicine, psychiatry, endocrinology, orthopedics, and physical therapy — their patients have one thing in common.

They don’t want to be in a doctor’s office. It means they have something, need something, or broke something.

It might be a treatable condition that’s merely inconvenient or a life-threatening event that’s flat-out terrifying.

Whatever it is, it pulls them out of their normal world. It can be a lonely, disorienting experience.

Sometimes the best thing a doctor can do is stay connected with the patient. “This is like a team sport,” Dr. Frank tells her patients. “I’m going to be your coach, but you’re the captain of the team.”

In some cases, she’ll ask the patient to message her on the portal after completing the daily or weekly exercises. That alone might motivate the patient — especially when she responds to their messages.

After all, nobody wants to let the coach down.
 

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

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Xanthelasma palpebrarum, characterized by yellowish plaques on the eyelids, is not associated with increased rates of dyslipidemia or cardiovascular disease.

METHODOLOGY:

• Researchers conducted a case-control study at a single tertiary care center in Israel and analyzed data from 35,452 individuals (mean age, 52.2 years; 69% men) who underwent medical screening from 2001 to 2020.
• They compared 203 patients with xanthelasma palpebrarum with 2030 individuals without the disease (control).
• Primary outcomes were prevalence of dyslipidemia and cardiovascular disease between the two groups.

TAKEAWAY:

• Lipid profiles were similar between the two groups, with no difference in total cholesterol, high- and low-density lipoprotein, and triglyceride levels (all P > .05).
• The prevalence of dyslipidemia was similar for patients with xanthelasma palpebrarum and controls (46% vs 42%, respectively; P = .29), as was the incidence of cardiovascular disease (8.9% vs 10%, respectively; P = .56).
• The incidence of diabetes (P = .13), cerebrovascular accidents (P > .99), ischemic heart disease (P = .73), and hypertension (P = .56) were not significantly different between the two groups.

IN PRACTICE:

“Our study conducted on a large population of individuals undergoing comprehensive ophthalmic and systemic screening tests did not find a significant association between xanthelasma palpebrarum and an increased prevalence of lipid abnormalities or cardiovascular disease,” the authors wrote.

SOURCE:

The study was led by Yael Lustig, MD, of the Goldschleger Eye Institute at Sheba Medical Center, in Ramat Gan, Israel. It was published online on August 5, 2024, in Ophthalmology.

LIMITATIONS:

The retrospective nature of the study and the single-center design may have limited the generalizability of the findings. The study population was self-selected, potentially introducing selection bias. Lack of histopathologic examination could have affected the accuracy of the diagnosis.

DISCLOSURES:

No funding sources were disclosed for this study. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Greater availability of peripheral tri-iodothyronine (T3), indicated by higher concentrations of free T3, T3, and T3/thyroxine (T4) ratio, is associated with increased liver fat content at baseline and a greater liver fat reduction following a dietary intervention known to reduce liver fat.

METHODOLOGY:

• Systemic hypothyroidism and subclinical hypothyroidism are proposed as independent risk factors for steatotic liver disease, but there are conflicting results in euthyroid individuals with normal thyroid function.
• Researchers investigated the association between thyroid function and intrahepatic lipids in 332 euthyroid individuals aged 50-80 years who reported limited alcohol consumption and had at least one condition for unhealthy aging (eg, cardiovascular disease).
• The analysis drew on a sub-cohort from the NutriAct trial, in which participants were randomly assigned to either an intervention group (diet rich in unsaturated fatty acids, plant protein, and fiber) or a control group (following the German Nutrition Society recommendations).
• The relationship between changes in intrahepatic lipid content and thyroid hormone parameters was evaluated in 243 individuals with data available at 12 months.

TAKEAWAY:

• Higher levels of free T3 and T3/T4 ratio were associated with increased liver fat content at baseline (P = .03 and P = .01, respectively).
• After 12 months, both the intervention and control groups showed reductions in liver fat content, along with similar reductions in free T3, total T3, T3/T4 ratio, and free T3/free T4 ratio (all P < .01).
• Thyroid stimulating hormone, T4, and free T4 levels remained stable in either group during the intervention.
• Participants who maintained higher T3 levels during the dietary intervention experienced a greater reduction in liver fat content over 12 months (Rho = −0.133; P = .039).

IN PRACTICE:

“A higher peripheral concentration of active THs [thyroid hormones] might reflect a compensatory mechanism in subjects with mildly increased IHL [intrahepatic lipid] content and early stages of MASLD [metabolic dysfunction–associated steatotic liver disease],” the authors wrote.

SOURCE:

The study was led by Miriam Sommer-Ballarini, Charité–Universitätsmedizin Berlin, Berlin, Germany. It was published online in the European Journal of Endocrinology.

LIMITATIONS:

Participants younger than 50 years of age and with severe hepatic disease, severe substance abuse, or active cancer were excluded, which may limit the generalizability of the findings. Because the study cohort had only mildly elevated median intrahepatic lipid content at baseline, it may not be suited to address the advanced stages of metabolic dysfunction–associated steatotic liver disease. The study’s findings are based on a specific dietary intervention, which may not be applicable to other dietary patterns or populations.

DISCLOSURES:

The Deutsche Forschungsgemeinschaft and German Federal Ministry for Education and Research funded this study. Some authors declared receiving funding, serving as consultants, or being employed by relevant private companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Greater availability of peripheral tri-iodothyronine (T3), indicated by higher concentrations of free T3, T3, and T3/thyroxine (T4) ratio, is associated with increased liver fat content at baseline and a greater liver fat reduction following a dietary intervention known to reduce liver fat.

METHODOLOGY:

• Systemic hypothyroidism and subclinical hypothyroidism are proposed as independent risk factors for steatotic liver disease, but there are conflicting results in euthyroid individuals with normal thyroid function.
• Researchers investigated the association between thyroid function and intrahepatic lipids in 332 euthyroid individuals aged 50-80 years who reported limited alcohol consumption and had at least one condition for unhealthy aging (eg, cardiovascular disease).
• The analysis drew on a sub-cohort from the NutriAct trial, in which participants were randomly assigned to either an intervention group (diet rich in unsaturated fatty acids, plant protein, and fiber) or a control group (following the German Nutrition Society recommendations).
• The relationship between changes in intrahepatic lipid content and thyroid hormone parameters was evaluated in 243 individuals with data available at 12 months.

TAKEAWAY:

• Higher levels of free T3 and T3/T4 ratio were associated with increased liver fat content at baseline (P = .03 and P = .01, respectively).
• After 12 months, both the intervention and control groups showed reductions in liver fat content, along with similar reductions in free T3, total T3, T3/T4 ratio, and free T3/free T4 ratio (all P < .01).
• Thyroid stimulating hormone, T4, and free T4 levels remained stable in either group during the intervention.
• Participants who maintained higher T3 levels during the dietary intervention experienced a greater reduction in liver fat content over 12 months (Rho = −0.133; P = .039).

IN PRACTICE:

“A higher peripheral concentration of active THs [thyroid hormones] might reflect a compensatory mechanism in subjects with mildly increased IHL [intrahepatic lipid] content and early stages of MASLD [metabolic dysfunction–associated steatotic liver disease],” the authors wrote.

SOURCE:

The study was led by Miriam Sommer-Ballarini, Charité–Universitätsmedizin Berlin, Berlin, Germany. It was published online in the European Journal of Endocrinology.

LIMITATIONS:

Participants younger than 50 years of age and with severe hepatic disease, severe substance abuse, or active cancer were excluded, which may limit the generalizability of the findings. Because the study cohort had only mildly elevated median intrahepatic lipid content at baseline, it may not be suited to address the advanced stages of metabolic dysfunction–associated steatotic liver disease. The study’s findings are based on a specific dietary intervention, which may not be applicable to other dietary patterns or populations.

DISCLOSURES:

The Deutsche Forschungsgemeinschaft and German Federal Ministry for Education and Research funded this study. Some authors declared receiving funding, serving as consultants, or being employed by relevant private companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Greater availability of peripheral tri-iodothyronine (T3), indicated by higher concentrations of free T3, T3, and T3/thyroxine (T4) ratio, is associated with increased liver fat content at baseline and a greater liver fat reduction following a dietary intervention known to reduce liver fat.

METHODOLOGY:

• Systemic hypothyroidism and subclinical hypothyroidism are proposed as independent risk factors for steatotic liver disease, but there are conflicting results in euthyroid individuals with normal thyroid function.
• Researchers investigated the association between thyroid function and intrahepatic lipids in 332 euthyroid individuals aged 50-80 years who reported limited alcohol consumption and had at least one condition for unhealthy aging (eg, cardiovascular disease).
• The analysis drew on a sub-cohort from the NutriAct trial, in which participants were randomly assigned to either an intervention group (diet rich in unsaturated fatty acids, plant protein, and fiber) or a control group (following the German Nutrition Society recommendations).
• The relationship between changes in intrahepatic lipid content and thyroid hormone parameters was evaluated in 243 individuals with data available at 12 months.

TAKEAWAY:

• Higher levels of free T3 and T3/T4 ratio were associated with increased liver fat content at baseline (P = .03 and P = .01, respectively).
• After 12 months, both the intervention and control groups showed reductions in liver fat content, along with similar reductions in free T3, total T3, T3/T4 ratio, and free T3/free T4 ratio (all P < .01).
• Thyroid stimulating hormone, T4, and free T4 levels remained stable in either group during the intervention.
• Participants who maintained higher T3 levels during the dietary intervention experienced a greater reduction in liver fat content over 12 months (Rho = −0.133; P = .039).

IN PRACTICE:

“A higher peripheral concentration of active THs [thyroid hormones] might reflect a compensatory mechanism in subjects with mildly increased IHL [intrahepatic lipid] content and early stages of MASLD [metabolic dysfunction–associated steatotic liver disease],” the authors wrote.

SOURCE:

The study was led by Miriam Sommer-Ballarini, Charité–Universitätsmedizin Berlin, Berlin, Germany. It was published online in the European Journal of Endocrinology.

LIMITATIONS:

Participants younger than 50 years of age and with severe hepatic disease, severe substance abuse, or active cancer were excluded, which may limit the generalizability of the findings. Because the study cohort had only mildly elevated median intrahepatic lipid content at baseline, it may not be suited to address the advanced stages of metabolic dysfunction–associated steatotic liver disease. The study’s findings are based on a specific dietary intervention, which may not be applicable to other dietary patterns or populations.

DISCLOSURES:

The Deutsche Forschungsgemeinschaft and German Federal Ministry for Education and Research funded this study. Some authors declared receiving funding, serving as consultants, or being employed by relevant private companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

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

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

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

TOPLINE:

Very high and very low levels of high-density lipoprotein cholesterol (HDL-C) are linked to a higher risk for kidney disease in women with type 2 diabetes (T2D), but not in men.

METHODOLOGY:

• Studies have reported a strong association between low HDL-C levels and the risk for diabetic kidney disease, but whether higher HDL-C levels can influence the risk for diabetic kidney disease remains unclear.
• Researchers conducted a cross-sectional observational study of 936 patients with T2D (mean age, about 60 years; 41% women; 33% with diabetic kidney disease) from the Endocrinology Department at the Jinhua Hospital between September 2020 and July 2021.
• To examine the relationship between HDL-C levels and the risk for diabetic kidney disease, researchers used logistic regression to assess the continuous and categorical associations and a restricted cubic spline curve to assess the nonlinear association.
• HDL-C levels were categorized into four groups, with 0.40-0.96 mmol/L corresponding to the lowest quartile and 1.32-6.27 mmol/L corresponding to the highest quartile.
• The researchers observed a U-shaped association between HDL-C levels and the risk for diabetic kidney disease (P_nonlinear = .010) and selected two threshold values of 0.95 and 1.54 mmol/L.

TAKEAWAY:

• The risk for diabetic kidney disease was higher when the HDL-C levels were < 0.95 mmol/L or > 1.54 mmol/L.
• Compared with patients with HDL-C levels in the range of 0.95-1.54 mmol/L, those with very high and very low HDL-C levels had a 128% and 77% increased risk for diabetic kidney disease, respectively.
• The association was significant in women (P = .006) and not in men (P = .054), after adjusting for confounding factors.
• HDL-C level as a continuous variable was not associated with the risk for kidney disease (P = .902).

IN PRACTICE:

“Although HDL-C is generally considered a cardiovascular protective factor, at very high levels, this protective effect does not seem to hold true and may be associated with an increased DKD [diabetic kidney disease] risk,” the authors wrote.

SOURCE:

This study was led by Huabin Wang, from the Department of Clinical Laboratory, Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China, and was published online in Scientific Reports.

LIMITATIONS:

The cross-sectional nature of the study limited the ability to establish a causal relationship between high HDL-C levels and the risk for diabetic kidney disease. The sample size of the study was relatively small at the higher end of the HDL-C concentration spectrum. Moreover, the study did not consider other potential confounding factors such as diet, sedentary lifestyle, obesity, genetic diseases, drug effects on HDL-C levels, and fluctuating estrogen levels, which could affect the overall findings.

DISCLOSURES:

The study was funded by the Department of Science and Technology of Zhejiang Province, China, and The Science and Technology Bureau of Jinhua City. The authors declared no competing interests.

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

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Recently, a patient of mine was hospitalized with chest pain. She was diagnosed with an acute coronary syndrome and started on a statin in addition to a beta-blocker, aspirin, and clopidogrel. After discharge, she had symptoms of dizziness and recurrent chest pain and her first thought was to stop the statin because she believed that her symptoms were statin-related side effects. I will cover a few areas where I think that there are some misunderstandings about statins.

Statins Are Not Bad For the Liver

When lovastatin first became available for prescription in the 1980s, frequent monitoring of transaminases was recommended. Patients and healthcare professionals became accustomed to frequent liver tests to monitor for statin toxicity, and to this day, some healthcare professionals still obtain liver function tests for this purpose.

But is there a reason to do this? Pfeffer and colleagues reported on the results of over 112,000 people enrolled in the West of Scotland Coronary Protection trial and found that the percentage of patients with any abnormal liver function test was similar (> 3 times the upper limit of normal for ALT) for patients taking pravastatin (1.4%) and for patients taking placebo (1.4%).¹ A panel of liver experts concurred that statin-associated transaminase elevations were not indicative of liver damage or dysfunction.² Furthermore, they noted that chronic liver disease and compensated cirrhosis were not contraindications to statin use.

In a small study, use of low-dose atorvastatin in patients with nonalcoholic steatohepatitis improved transaminase values in 75% of patients and liver steatosis and nonalcoholic fatty liver disease activity scores were significantly improved on biopsy in most of the patients.³ The US Food and Drug Administration (FDA) removed the recommendation for routine regular monitoring of liver function for patients on statins in 2012.⁴

Statins Do Not Cause Muscle Pain in Most Patients

Most muscle pain occurring in patients on statins is not due to the statin although patient concerns about muscle pain are common. In a meta-analysis of 19 large statin trials, 27.1% of participants treated with a statin reported at least one episode of muscle pain or weakness during a median of 4.3 years, compared with 26.6% of participants treated with placebo.⁵ Muscle pain for any reason is common, and patients on statins may stop therapy because of the symptoms.

Cohen and colleagues performed a survey of past and current statin users, asking about muscle symptoms.⁶ Muscle-related side effects were reported by 60% of former statin users and 25% of current users.

Herrett and colleagues performed an extensive series of n-of-1 trials involving 200 patients who had stopped or were considering stopping statins because of muscle symptoms.⁷ Participants received either 2-month blocks of atorvastatin 20 mg or 2-month blocks of placebo, six times. They rated their muscle symptoms on a visual analogue scale at the end of each block. There was no difference in muscle symptom scores between the statin and placebo periods.

Wood and colleagues took it a step further when they planned an n-of-1 trial that included statin, placebo, and no treatment.⁸ Each participant received four bottles of atorvastatin 20 mg, four bottles of placebo, and four empty bottles. Each month they used treatment from the bottles based on a random sequence and reported daily symptom scores. The mean symptom intensity score was 8.0 during no-tablet months, 15.4 during placebo months (P < .001, compared with no-tablet months), and 16.3 during statin months (P < .001, compared with no-tablet months; P = .39, compared with placebo).
 

Statins Are Likely Helpful In the Very Elderly

Should we be using statins for primary prevention in our very old patients? For many years the answer was generally “no” on the basis of a lack of evidence. Patients in their 80s often were not included in clinical trials. The much used American Heart Association risk calculator stops at age 79. Given the prevalence of coronary artery disease in patients as they reach their 80s, wouldn’t primary prevention really be secondary prevention? Xu and colleagues in a recent study compared outcomes for patients who were treated with statins for primary prevention with a group who were not. In the patients aged 75-84 there was a risk reduction for major cardiovascular events of 1.2% over 5 years, and for those 85 and older the risk reduction was 4.4%. Importantly, there were no significantly increased risks for myopathies and liver dysfunction in either age group.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and he serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at imnews@mdedge.com.

References

1. Pfeffer MA et al. Circulation. 2002;105(20):2341-6.

2. Cohen DE et al. Am J Cardiol. 2006;97(8A):77C-81C.

3. Hyogo H et al. Metabolism. 2008;57(12):1711-8.

4. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012 Feb 28.

5. Cholesterol Treatment Trialists’ Collaboration. Lancet. 2022;400(10355):832-45.

6. Cohen JD et al. J Clin Lipidol. 2012;6(3):208-15.

7. Herrett E et al. BMJ. 2021 Feb 24;372:n1355.

8. Wood FA et al. N Engl J Med. 2020;383(22):2182-4.

9. Xu W et al. Ann Intern Med. 2024;177(6):701-10.

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

Do people who drink alcohol in moderation have a greater risk of early death than people who abstain? For years, a drink or two a day appeared to be linked to health benefits. But recently, scientists pointed out flaws in some of the studies that led to those conclusions, and public health warnings have escalated recently that there may be no safe level of alcohol consumption.

Now, yet another research analysis points toward that newer conclusion – that people who drink moderately do not necessarily live longer than people who abstain. The latest results are important because the researchers delved deep into data about people who previously drank but later quit, possibly due to health problems.

“That makes people who continue to drink look much healthier by comparison,” said Tim Stockwell, PhD, lead author of this latest analysis and a scientist with the Canadian Institute for Substance Use Research at the University of Victoria, in a statement.

The findings were published in the Journal of Studies on Alcohol and Drugs.

The key to their conclusion that drinking isn’t linked to longer life is based yet again on who moderate drinkers are compared to, Dr. Stockwell and his colleagues wrote.

For the study, researchers defined “low volume drinking” as having between one drink per week and up to two drinks per day. When researchers carefully excluded people who were former drinkers and only included data for people who were younger than 55 when they joined research studies, the abstainers and low-volume drinkers had similar risks of early death. But when the former drinkers were included in the abstainer group, the low-volume drinkers appeared to have a reduced risk of death.

When researchers define which people are included in a research analysis based on criteria that don’t reflect subtle but important population characteristics, the problem is called “selection bias.” 

“Studies with life-time selection biases may create misleading positive health associations. These biases pervade the field of alcohol epidemiology and can confuse communications about health risks,” the authors concluded.

They called for improvements in future research studies to better evaluate drinking levels that may influence health outcomes, and also noted one of their exploratory analyses suggested a need to delve deeper into the effects of other outside variables such as smoking and socioeconomic status. 
 

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

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

The market for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to lower cholesterol is taking off with several new drugs being introduced or nearing the market, which will increase competition and enable more patients to reach low-density lipoprotein (LDL) goals, experts said.

One new anti-PCSK9 agent — lerodalcibep from LIB Therapeutics — is a small protein molecule, which is expected to reach the market by early 2026. It is being positioned as a step forward from the two monoclonal antibody products already available — evolocumab (Repatha; Amgen) and alirocumab (Praluent; Sanofi/Regeneron).

The new option can be given less frequently than the antibodies with a once-a-month injection instead of every 2 weeks. It also does not need to be kept refrigerated like the antibodies, Evan Stein, MD, chief scientific and operating officer of LIB Therapeutics, said in an interview.

Two phase 3 trials have recently been reported, showing impressive reductions in LDL in patients already taking statins.
 

The LIBerate Trials

The LIBerate-HR trial, published in JAMA Cardiology, involved 922 patients who still had LDL above target despite taking maximally tolerated statin therapy plus other lipid-lowering agents in some cases.

The trial found a time-averaged mean reduction in LDL cholesterol of 62%.

“This large reduction resulted in more than 90% of patients reaching the new lower LDL targets set in recent guidelines of less than 55 mg/dL for patients with cardiovascular disease or at very high risk, and less than 70 mg/dL in patients at risk,” said Stein.

Another phase 3 trial, LIBerate-CVD, has also shown reductions in LDL cholesterol levels of more than 60% in patients at high risk for cardiovascular disease on maximally tolerated statins.

LIB Therapeutics plans to file approval applications for lerodalcibep in the United States and Europe later this year.
 

A Crowded Field

Dr. Stein said PCSK9 inhibitors have been underused so far, but this is starting to change.

“The monoclonal antibodies were way overpriced costing around $14,000 per year when they were first introduced, which resulted in huge pushback from insurance companies,” Dr. Stein said, which made the drugs difficult to prescribe. “Then a few years ago, the price dropped a bit, and now they’re probably running at about $4000 per year, which made them more accessible.”

He said the market is now rapidly taking off. Lerodalcibep will compete in the anti-PCSK9 market with not only the two monoclonal antibodies but also with the new short-interfering RNA agent, inclisiran (Leqvio; Novartis) , a novel injectable agent that is given just twice a year but has to be administered at a medical facility.

Despite the crowded field, there appears to be plenty of room in the market. “Last year, growth was just under 40%. The first quarter of this year, it has increased by 44%. While the introduction of inclisiran has added to this growth, it hasn’t dented the sales of the existing monoclonal antibodies,” said Dr. Stein.

He estimates that the anti-PCSK9 market will reach $3 billion globally this year, and by the time lerodalcibep is launched, it could be worth $5 billion.

As well as inclisiran and lerodalcibep, there are other innovations in the anti-PCSK9 field in development, with oral drugs now also in the pipeline. The first one of these, in development by Merck, is in early phase 3 trials, and AstraZeneca has an oral agent in earlier development.
 

Enthusiastic Response

Other experts in the lipid field are also enthusiastic about new developments in the PCSK9s.

Jorge Plutzky, MD, director of preventive cardiology at Brigham and Women’s Hospital in Boston, said he welcomes the prospect of new approaches to PCSK9 inhibition.

“The increase in the number of safe, effective tools for LDL lowering, whether through PCSK9 or other targets, is inevitably beneficial for patients and the field,” he said during an interview.

Dr. Plutzky pointed out that although the current agents are effective, cost and coverage remain issues despite some recent progress in these areas, and new agents will increase competition and should hopefully drive prices down. Having a variety of dosing methods and frequencies provides more options for patients to find the one that works best for them.

Lerodalcibep’s once-monthly dosing schedule and the lack of need for refrigeration may be appreciated by some patients, he said, particularly those who need to travel for long periods.

Connie Newman, MD, adjunct professor of medicine at NYU School of Medicine, New York City, said there is plenty of room in the market to accommodate patient’s needs and preferences.

“Despite the US FDA approval of three medications that target PCSK9, there is a need for more anti-PCSK9 agents that reduce LDL and cardiovascular events,” she said. “In the US alone, 25% of adults have LDL levels of 130 mg/dL and above. Of all the non-statin therapies, medications targeting PCSK9 produce the greatest reduction in LDL. However, some patients may not tolerate one or more of the medications available or may prefer a monthly injection of lower volume.”

Dr. Newman said she believes there will still be a market for injectable formulations of PCSK9 inhibitors in the future, even if oral formulations are approved.

“Oral formulations usually require more frequent administration. Some people prefer longer-acting medications that can be taken less often. This might lead to better adherence,” she said.

Dr. Stein said he agrees there will always be room for different options. “And you only have to look at what is happening with the weight loss drugs to see that there is a market for injectables.” The ability to get patients to the new, more aggressive LDL goals is what is important, he added. “These drugs do that, and offering patients a choice of agents and delivery mechanisms is helpful.”

A version of this article appeared on Medscape.com.

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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

TOPLINE:

Over the past 20 years in Denmark, the incidence of type 2 diabetes–related outcomes and many treatment-related harms have both decreased without increased medication expenses despite an aging and more comorbid population; however, challenges remain.

METHODOLOGY:

• Analysis of data from 461,805 individuals in the Danish population with type 2 diabetes between 2002 and 2020.
• Multivariate analyses adjusted for potential confounders, including age, sex, and socioeconomic status.

TAKEAWAY:

• The population grew 2.7-fold from 2002 to 2020 (n = 113,105 to 306,962), the median age increased from 66 to 68 years, and the mean number of diseases per person increased from 5.2 to 8.8, with an increase in Charlson Comorbidity Index from 1.78 to 1.93.
• After adjustments, mortality per 1000 person-years decreased by 28% from 2002 to 2020, with the largest risk reduction, 63%, in acute myocardial infarction.
• The mean number of annually redeemed medications per person increased from 8.1 to 9.0, with statin and antihypertensive use increasing to 65% and 69%, respectively.
• Antiplatelet medication (aspirin and clopidogrel) use peaked at 48% in 2009 and dropped to 31% in 2020.
• Anticoagulant (warfarin and direct-acting oral anticoagulants) use gradually increased from 5% in 2002 to 14% in 2020.
• For glucose-lowering treatment, there was a shift away from using sulfonylureas to metformin and other medications.
• Diagnoses of hypoglycemia, falls, and gastric bleeding decreased over the study period, but incidences of volume depletion, ketoacidosis, infections, and electrolyte imbalances requiring hospitalization increased.
• Cumulative expenses for the population increased from €132,000,000 to €327,000,000 (approximately $144,406,680 to $357,734,730), corresponding to a 148% increase over the study period.
• However, the average medication cost per individual was 8% less in 2020 compared with 2002 despite increasing medication use, mainly driven by reduced costs of antiplatelets, antihypertensives, and statins, among others.
• In contrast, expenses for glucose-lowering medications have gradually increased, with the average more than doubling (138% increase) from €220 ($240) in 2002 to €524 ($573) in 2020.

IN PRACTICE:

“Although these trends suggest improvements in rational pharmacotherapy, they cannot be solely attributed to improved pharmacotherapy and appear to be multifactorial,” the authors wrote.

“Advancements in diabetes management have improved the balance between medication benefits, harms, and costs ... Remaining challenges, such as an increased risk of ketoacidosis and electrolyte imbalances as well as rising costs for glucose-lowering medications, highlight the importance of individualized treatment and continuous risk-benefits evaluations,” they added.
 

SOURCE:

This study was conducted by Karl Sebastian Johansson, of the Department of Clinical Pharmacology, Copenhagen University Hospital, Copenhagen, Denmark, and colleagues and was published online in Diabetes Care.

LIMITATIONS:

Analysis was confined to events diagnosed in hospital-based inpatient and outpatient settings, not primary healthcare. Only predefined adverse events were analyzed.

DISCLOSURES:

The study was funded by the Capital Region of Denmark. The authors reported no potential conflicts of interest relevant to this article.

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