Obesity

TOPLINE:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. 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:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. 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:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. 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.

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition 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.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition 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.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition 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:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Bariatric surgery may lower the risk for breast cancer in women with obesity, particularly in premenopausal women and in women with high insulin levels at baseline.

METHODOLOGY:

• Previous research suggests that bariatric surgery is associated with a lower risk for cancer in people with obesity, as well as female-specific cancers in women with obesity, especially those with higher baseline insulin levels. But there is a need for large prospective studies with more detailed patient information.
• The current secondary analysis included 2867 matched women (mean age, 48 years) from a prospective nonrandomized Swedish trial, which recruited men and women who had obesity between 1987 and 2001.
• Overall, 1420 women underwent bariatric surgery, and 1447 received usual care.
• Median baseline insulin levels were 15.8 μIU/L. In the surgery group, 68.3% of patients had vertical banded gastroplasty, 18.3% underwent gastric banding, and 13.4% underwent gastric bypass.
• The main outcome was breast cancer incidence, as identified from Swedish National Cancer Registry.

TAKEAWAY:

• Over a median follow-up of 23.9 years, 66 breast cancer events occurred in the surgery group and 88 in the usual care group (P = .02).
• Bariatric surgery was associated with a 33% lower risk for breast cancer (adjusted hazard ratio [aHR], 0.67), after excluding cases that occurred within the first 3 years (to account for any undiagnosed breast cancer at baseline) and adjusting for age, body mass index, alcohol, and smoking status.
• Looking at the menopausal status at baseline, bariatric surgery was associated with a reduced risk for breast cancer in premenopausal women (aHR, 0.64) but not postmenopausal women (aHR, 0.84; 95% CI, 0.49-1.45; P = .54).
• Bariatric surgery was also associated with a lower risk for breast cancer in women with baseline insulin levels above the median (aHR, 0.55) than in those with baseline insulin levels below the median (aHR, 1.01).

IN PRACTICE:

“The surgical treatment benefit was predominantly seen in women with hyperinsulinemia, suggesting insulin may be used as a predictor of treatment effect,” the authors wrote. Authors of an accompanying editorial, however, cautioned that “it is not known if insulin levels or insulin resistance are true biomarkers of breast cancer risk in patients with obesity undergoing bariatric surgery” and urged further research into underlying biological mechanisms.

SOURCE:

This study, led by Felipe M. Kristensson, MD, from Institute of Medicine, Department of Molecular and Clinical Medicine, the Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden, was published online in JAMA Surgery. The accompanying editorial was led by Swati A. Kulkarni, MD, of the Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago.

LIMITATIONS:

The study was not randomized. Breast cancer was not a predefined outcome of the main trial. Most patients underwent vertical banded gastroplasty, which is rarely used and could limit applicability of the results; however, vertical banded gastroplasty results in weight loss similar to that observed after sleeve gastrectomy. Follow-up values for insulin and insulin resistance were not available. The researchers noted significant differences in 12 out of 17 baseline characteristics between the two groups, including a larger proportion of postmenopausal women in the usual care group.

DISCLOSURES:

This study was supported by the Swedish state, Swedish Research Council, the Health & Medical Care Committee of the Region Västra Götaland, and the Adlerbert Research Foundation. The authors did not report any conflicts of interest.

A version of this article appeared on Medscape.com.

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

STOCKHOLM — Improvements in kidney function outcomes observed with glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes extend to patients who are overweight or obese but don›t yet have type 2 diabetes, new research shows.

“These data are important because they are the first data to suggest a kidney benefit of semaglutide in this patient population in the absence of diabetes,” lead author Helen M. Colhoun, MD, of the Institute of Genetics and Cancer, University of Edinburgh, Scotland, United Kingdom, told this news organization.

“This is a population at high risk of chronic kidney disease with an increased need for kidney protection,” she said.

The late-breaking study was presented this week at the 61st European Renal Association (ERA) Congress 2024 and simultaneously published in Nature Medicine.
 

SELECT Trial Patients Without Diabetes

The findings are from a secondary analysis of the randomized SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity) trial, which evaluated cardiovascular outcomes of semaglutide treatment among 17,604 adults with preexisting cardiovascular disease who were overweight or obese — but did not have diabetes.

For its primary endpoint, the trial showed semaglutide was associated with a 20% reduction in major adverse cardiovascular events compared with placebo.

With obesity also associated with a significantly increased risk of chronic kidney disease — and the headline-making FLOW trial, also presented at the congress, showing key benefits of semaglutide in improving kidney function in people with CKD and type 2 diabetes the secondary analysis of SELECT was conducted to investigate whether those kidney benefits extended to people without type 2 diabetes.

Patients were randomized 1:1 to once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. Baseline patient characteristics were well-balanced, including kidney function and albuminuria status.

The primary endpoint for the analysis was a nephropathy composite of time from randomization to the first occurrence of death from kidney causes; initiation of chronic kidney replacement therapy; onset of persistent estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m²; persistent ≥ 50% reduction in eGFR compared with baseline; or onset of persistent macroalbuminuria.

With a median follow-up of 182 weeks, the results showed that the semaglutide group was significantly less likely to develop the primary composite endpoint compared with the placebo group (1.8% vs 2.2%; hazard ratio [HR], 0.78; P = .02).

A significantly reduced decline in eGFR in the semaglutide group was observed at a prespecified 104-week time point, with a treatment effect of 0.75 mL/min/1.73 m² (P < .001), and the effect was more pronounced among participants with baseline eGFR < 60 mL/min/1.73 m² (P < .001). 

Furthermore, those in the semaglutide group had a significantly lower proportionate increase in urinary albumin-to-creatinine ratio (UACR) compared with placebo (–10.7%; P < .001) at the prespecified 104 weeks, with a net treatment benefit of –27.2% and –31.4% among those with randomization to UACR 30 to < 300 mg/g and 2300 mg/g, respectively.

Improvements varied according to baseline UACR status and were more pronounced among those with macroalbuminuria, at –8.1% for those with normoalbuminuria (n = 14,848), –27% for microalbuminuria (n = 1968), and –31% for macroalbuminuria (n = 325).

There were no reports of acute kidney injury associated with semaglutide, regardless of baseline eGFR. 

“We were hopeful that there would be similar benefits as those observed in the diabetes studies, but there are differences in kidney disease among those with and without type 2 diabetes, so we weren’t sure,” Dr. Colhoun told this news organization.
 

Benefits the Result of Weight Loss or Something Else?

Considering the beneficial effects of semaglutide on weight loss, underscored in an analysis also published this month that showed a mean 10.2% reduction in weight sustained for up to 4  years, a key question is whether the kidney benefits are a direct result of weight loss — or the drug mechanism or something else.

But Dr. Colhoun said the role of weight loss in terms of the kidney benefits is still uncertain, particularly considering the various other factors, including cardiometabolic improvements, which could also have an effect.

“It’s a very difficult question to answer,” she said. “We did do a mediation exploratory analysis suggesting a substantial part of the effect might be due to the weight change, but it’s difficult to demonstrate that because you have weight change going on in the placebo arm as well, but for different reasons,” she said.

“So, I would say the data suggest there is some component of this that is attributable to weight, but we certainly can’t attribute all of the [effects] to weight change.”

Small studies involving animals have shown a direct effect of semaglutide on kidney hemodynamics “but they’re small and not definitive,” Dr. Colhoun added.

And although weight loss achieved through other measures such as lifestyle changes show a small benefit on eGFR, “interestingly, those studies showed no effect at all on albuminuria, whereas we see a really substantial effect on albuminuria with semaglutide,” Dr. Colhoun said.

Studies of weight loss through bariatric surgery have shown kidney benefits; however, those were in the context of type 2 diabetes, unlike the current analysis.

In terms of whether the benefits may extend to tirzepatide, the dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, increasingly used in weight loss, results from another secondary analysis also show encouraging kidney benefits in people with type 2 diabetes, and there is ongoing research in patients with type 2 diabetes and those with obesity without diabetes, Dr. Colhoun noted.
 

Primary Prevention of CKD?

Limitations of the current analysis include that only about a fifth of participants in SELECT had an eGFR < 60  mL/min/1.73 m² or UACR ≥ 30 mg/g at baseline, suggesting a relatively low proportion of participants with kidney disease. 

Importantly, however, the kidney benefits observed in patients who are at such high risk of kidney disease but do not yet have diabetes or CKD, is encouraging, said Alberto Ortiz, MD, PhD, commenting on the study. Dr. Ortiz is chief of nephrology and the Hypertension Renal Unit, Health Research Institute of the Jiménez Díaz Foundation, Madrid, Spain.

“It is especially significant that protection was observed in participants with an eGFR > 60 mL/min/1.73 m² and across UACR categories, ie, including people without CKD at baseline, in whom it appeared to decrease the incidence of de novo CKD,” Dr. Ortiz told this news organization.

“This suggests a potential role in primary prevention of CKD in this population,” he said.

To further investigate this, he said, “It would have been extremely interesting to assess whether there is a potential role for primary prevention of CKD in people without baseline CKD by assessing subgroup results for the no-CKD, low-risk KDIGO [Kidney Disease: Improving Global Outcomes] category [of patients].”

SELECT was funded by Novo Nordisk. Dr. Colhoun has reported consulting, research, and/or other relationships with Novo Nordisk, Bayer, Sanofi, Roche, and IQVIA. Dr. Ortiz has reported being a member of the European Renal Association council and Madrid Society of Nephrology (SOMANE), which developed a document in 2022 on the treatment of diabetic kidney disease sponsored by Novo Nordisk. He also reported collaborating with companies developing drugs for kidney disease.

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

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.