Obesity

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant 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:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant 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:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant 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.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), bariatric surgery appears to carry a lower risk for mortality after 5 years than treatment with pharmacologic therapies such as glucagon-like peptide 1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors, new study results showed.

In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.

“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.

Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.

These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”

 

Comparing Bariatric Interventions and Pharmacologic Treatments

The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).

In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.

When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.

In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.

When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.

Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.

Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.

“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”

 

Considering a Multidisciplinary Approach to MASLD Treatment

Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.

“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”

Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.

“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”

Ghani, Ali, and Schwenger reported no relevant disclosures.

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

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), bariatric surgery appears to carry a lower risk for mortality after 5 years than treatment with pharmacologic therapies such as glucagon-like peptide 1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors, new study results showed.

In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.

“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.

Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.

These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”

 

Comparing Bariatric Interventions and Pharmacologic Treatments

The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).

In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.

When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.

In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.

When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.

Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.

Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.

“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”

 

Considering a Multidisciplinary Approach to MASLD Treatment

Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.

“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”

Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.

“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”

Ghani, Ali, and Schwenger reported no relevant disclosures.

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

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), bariatric surgery appears to carry a lower risk for mortality after 5 years than treatment with pharmacologic therapies such as glucagon-like peptide 1 (GLP-1) receptor agonists or sodium-glucose cotransporter 2 (SGLT2) inhibitors, new study results showed.

In a separate analysis of data from the same study, researchers also found that bariatric surgery alone had lower risks for major adverse cardiovascular events (MACEs) than GLP-1 or SGLT2 inhibitor use or a combination of surgery and medications.

“While weight loss medications have demonstrated notable success, especially in managing diabetes and aiding weight loss, bariatric surgery offers more significant and varied benefits for weight and metabolic health, making it a better option for some patients,” said Leith Ghani, DO, an internal medicine resident at The University of Arizona College of Medicine – Phoenix.

Ghani presented the findings about mortality at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD). His co-author and fellow internal medicine resident Qumber Ali, DO, presented the findings about MACEs.

These findings highlight “the need for personalized treatment plans, allowing the decision between surgery and medication to be customized according to each patient’s specific situation and health goals,” Ghani said. “It also emphasizes the importance of a multidisciplinary approach to patient management.”

 

Comparing Bariatric Interventions and Pharmacologic Treatments

The retrospective, multicenter study of hospital admissions data from the Banner Health system in Phoenix included more than 8600 patients who had MASLD-related diagnostic codes and metabolic criteria. Patients were divided into four groups according to the treatment they received: Bariatric surgery alone (5.8%), GLP-1 medications (39.3%), SGLT2 inhibitor medications (23.4%), or a combination of surgery and medications (31.5%).

In the mortality analysis, Ghani and colleagues looked at data for patients who died between 12 and 60 months after surgery or starting medication. They found that patients who underwent bariatric surgery had a significantly higher chance of survival at 5 years.

When compared to bariatric surgery, the adjusted hazard ratio (aHR) for GLP-1 medications was 2.99, followed by an aHR of 2.96 for SGLT2 inhibitor medications, and an aHR of 1.78 for a combination of treatments.

In the MACE analysis, Ali and colleagues looked at data for patients who were followed for 12 months or more after intervention or initiation of treatment, identifying MACE diagnostic codes for coronary artery disease, cerebrovascular disease, and congestive heart failure. They found that patients who underwent bariatric surgery alone had a significantly lower rate of MACEs.

When compared to bariatric surgery, the aHR was 1.83 for GLP-1 medications, 1.72 for SGLT2 inhibitor medications, and 1.91 for a combination of treatments.

Regarding both analyses, patients taking GLP-1 or SGLT2 inhibitor medications may face higher risks for mortality or serious heart problems due to existing metabolic disorders or heart disease, Ali said.

Future studies could look at other risk factors that make these patients more vulnerable, he added. For instance, factors related to body mass index, glucose control, other medications, different clinical settings, and race/ethnicity can contribute to different treatment responses, as could the decision to take medication or undergo surgery in the first place.

“This emphasizes the need for additional, prospective randomized clinical trial research to explore why these differences exist,” Ali said. “While progress has been made, there is still much to learn about the optimal management of patients with metabolic and cardiovascular disorders.”

 

Considering a Multidisciplinary Approach to MASLD Treatment

Ghani and Ali also called for personalized treatment plans for metabolic-related disorders such as MASLD, as well as strong communication among specialists and with patients about the benefits and risks of choosing certain medications and procedures.

“Bariatric surgery is not a universal solution, and not all patients are suitable for surgery,” Ghani said. “We also can’t say at this point that drug treatments are worse than bariatric surgery. The effectiveness of these therapies can vary greatly depending on a patient’s health, lifestyle, and preferences.”

Looking ahead, MASLD studies should investigate long-term weight loss seen with bariatric surgery and different medications, said Katherine Schwenger, PhD, RD, a scientific associate at Toronto General Hospital in Toronto, Ontario, Canada.

“GLP-1s are a hot topic right now,” said Schwenger, who wasn’t involved with the study. But “we need to look at factors such as the longevity of weight loss. It’s hard to beat the success and sustainability of bariatric surgery.”

Ghani, Ali, and Schwenger reported no relevant disclosures.

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

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

If you’ve ever taken a red-eye flight you have probably received a little packet of items the airline hopes will make your night flight more comfortable. If you had shelled out for “extra leg room” or “more comfort” seating, your little kit may have included some one-size-never-fits-all socks, a toothbrush large enough to brush one tooth at a time, and a miniature tube of toothpaste the GEICO gecko would laugh at. I have no personal knowledge what the folks in first class are getting, but I suspect it comes in a calf skin Gucci pouch. But, regardless of where you are sitting, at a minimum your night comfort kit will come with an eye mask and ear plugs. Unfortunately, these freebies are wasted on me because I already use a sleep mask every night and simply turn off my hearing aids to mute the noise. But I appreciate their effort.

Light and sound are well-known sleep disruptors. Temperature gets less attention, but is nonetheless a potent contributor to a poor night’s sleep in my experience. Just by chance while I was recovering from my most recent jet lag, I encountered two papers from investigators who were curious about the association between healthy sleep and ambient light and noise.

 

The first paper looked at the relationship between artificial light at night (ALAN) and the incidence of insomnia. Looking at more than 300 Chinese cities, the investigators measured ALAN using satellite images and correlated the data with insomnia-related posts on social media. The researchers found when ALAN increased insomnia, related posts also increased. Not surprisingly, this relationship was greater in less populated cities during extreme temperatures and when air quality was poor. 

The second paper came from University of Texas at Houston. Using Fitbit data from more than 3000 adolescents, the researchers looked for correlations between blood pressure, sleep health, and “median nighttime anthropogenic noise levels by ZIP code.” Turns out the Federal Highway Administration has a readily available map of these noise levels. 

What the investigators found was that adequate sleep significantly reduces the risk of hypertension in adolescents. Not an unexpected finding to an ex-pediatrician like myself who is obsessed with the importance of sleep deprivation. However, the investigators and I were surprised that they had found no association between neighborhood noise alone or in combination with sleep health. I still suspect there is an association lurking there in the weeds of their data, but obviously it is not robust enough to float to the surface. It may be that in an acute situation noise can contribute to hypertension, but over time individuals adjust to the new sound level and their blood pressure settles down. Sleep is such a critical factor that it is not something our cardiovascular system can adapt to so easily. For various reasons most of us may already be functioning at the margins of sleep deprivation.

How then do we respond to observations by these two research teams? Do we take an approach similar to that the airlines have taken and prescribe, hand out, or sell ear plugs and sleep masks to every patient, or at least those with hypertension? This is what we could call the put-the-onus-on-the-patient approach, which seems to be the default when we lack the political will to take a bolder step.

The other path we could call the socio-environmental approach. The airlines have made a passing attempt at this by turning the cabin lights down on red-eye flights. I recently wrote about the “exposome,” which some investigators define as the total non-genetic exposures an individual endures during a lifetime and which in many situations has a negative effect on the individual’s health. These two papers clearly demonstrate that noise and nighttime artificial light are potent features of an uncountable number of individuals’ exposomes.

Noise and artificial light are both things that as a society we have the power to control if we could only muster up the political will to do so. Unfortunately, it is going to require something far beyond these two relatively obscure studies to move the needle in the direction of a healthier population. It’s is not a stretch to put obesity and the attention deficit phenomenon under this same umbrella where our society needs to look at itself for the answers.

 

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

If you’ve ever taken a red-eye flight you have probably received a little packet of items the airline hopes will make your night flight more comfortable. If you had shelled out for “extra leg room” or “more comfort” seating, your little kit may have included some one-size-never-fits-all socks, a toothbrush large enough to brush one tooth at a time, and a miniature tube of toothpaste the GEICO gecko would laugh at. I have no personal knowledge what the folks in first class are getting, but I suspect it comes in a calf skin Gucci pouch. But, regardless of where you are sitting, at a minimum your night comfort kit will come with an eye mask and ear plugs. Unfortunately, these freebies are wasted on me because I already use a sleep mask every night and simply turn off my hearing aids to mute the noise. But I appreciate their effort.

Light and sound are well-known sleep disruptors. Temperature gets less attention, but is nonetheless a potent contributor to a poor night’s sleep in my experience. Just by chance while I was recovering from my most recent jet lag, I encountered two papers from investigators who were curious about the association between healthy sleep and ambient light and noise.

 

The first paper looked at the relationship between artificial light at night (ALAN) and the incidence of insomnia. Looking at more than 300 Chinese cities, the investigators measured ALAN using satellite images and correlated the data with insomnia-related posts on social media. The researchers found when ALAN increased insomnia, related posts also increased. Not surprisingly, this relationship was greater in less populated cities during extreme temperatures and when air quality was poor. 

The second paper came from University of Texas at Houston. Using Fitbit data from more than 3000 adolescents, the researchers looked for correlations between blood pressure, sleep health, and “median nighttime anthropogenic noise levels by ZIP code.” Turns out the Federal Highway Administration has a readily available map of these noise levels. 

What the investigators found was that adequate sleep significantly reduces the risk of hypertension in adolescents. Not an unexpected finding to an ex-pediatrician like myself who is obsessed with the importance of sleep deprivation. However, the investigators and I were surprised that they had found no association between neighborhood noise alone or in combination with sleep health. I still suspect there is an association lurking there in the weeds of their data, but obviously it is not robust enough to float to the surface. It may be that in an acute situation noise can contribute to hypertension, but over time individuals adjust to the new sound level and their blood pressure settles down. Sleep is such a critical factor that it is not something our cardiovascular system can adapt to so easily. For various reasons most of us may already be functioning at the margins of sleep deprivation.

How then do we respond to observations by these two research teams? Do we take an approach similar to that the airlines have taken and prescribe, hand out, or sell ear plugs and sleep masks to every patient, or at least those with hypertension? This is what we could call the put-the-onus-on-the-patient approach, which seems to be the default when we lack the political will to take a bolder step.

The other path we could call the socio-environmental approach. The airlines have made a passing attempt at this by turning the cabin lights down on red-eye flights. I recently wrote about the “exposome,” which some investigators define as the total non-genetic exposures an individual endures during a lifetime and which in many situations has a negative effect on the individual’s health. These two papers clearly demonstrate that noise and nighttime artificial light are potent features of an uncountable number of individuals’ exposomes.

Noise and artificial light are both things that as a society we have the power to control if we could only muster up the political will to do so. Unfortunately, it is going to require something far beyond these two relatively obscure studies to move the needle in the direction of a healthier population. It’s is not a stretch to put obesity and the attention deficit phenomenon under this same umbrella where our society needs to look at itself for the answers.

 

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

If you’ve ever taken a red-eye flight you have probably received a little packet of items the airline hopes will make your night flight more comfortable. If you had shelled out for “extra leg room” or “more comfort” seating, your little kit may have included some one-size-never-fits-all socks, a toothbrush large enough to brush one tooth at a time, and a miniature tube of toothpaste the GEICO gecko would laugh at. I have no personal knowledge what the folks in first class are getting, but I suspect it comes in a calf skin Gucci pouch. But, regardless of where you are sitting, at a minimum your night comfort kit will come with an eye mask and ear plugs. Unfortunately, these freebies are wasted on me because I already use a sleep mask every night and simply turn off my hearing aids to mute the noise. But I appreciate their effort.

Light and sound are well-known sleep disruptors. Temperature gets less attention, but is nonetheless a potent contributor to a poor night’s sleep in my experience. Just by chance while I was recovering from my most recent jet lag, I encountered two papers from investigators who were curious about the association between healthy sleep and ambient light and noise.

 

The first paper looked at the relationship between artificial light at night (ALAN) and the incidence of insomnia. Looking at more than 300 Chinese cities, the investigators measured ALAN using satellite images and correlated the data with insomnia-related posts on social media. The researchers found when ALAN increased insomnia, related posts also increased. Not surprisingly, this relationship was greater in less populated cities during extreme temperatures and when air quality was poor. 

The second paper came from University of Texas at Houston. Using Fitbit data from more than 3000 adolescents, the researchers looked for correlations between blood pressure, sleep health, and “median nighttime anthropogenic noise levels by ZIP code.” Turns out the Federal Highway Administration has a readily available map of these noise levels. 

What the investigators found was that adequate sleep significantly reduces the risk of hypertension in adolescents. Not an unexpected finding to an ex-pediatrician like myself who is obsessed with the importance of sleep deprivation. However, the investigators and I were surprised that they had found no association between neighborhood noise alone or in combination with sleep health. I still suspect there is an association lurking there in the weeds of their data, but obviously it is not robust enough to float to the surface. It may be that in an acute situation noise can contribute to hypertension, but over time individuals adjust to the new sound level and their blood pressure settles down. Sleep is such a critical factor that it is not something our cardiovascular system can adapt to so easily. For various reasons most of us may already be functioning at the margins of sleep deprivation.

How then do we respond to observations by these two research teams? Do we take an approach similar to that the airlines have taken and prescribe, hand out, or sell ear plugs and sleep masks to every patient, or at least those with hypertension? This is what we could call the put-the-onus-on-the-patient approach, which seems to be the default when we lack the political will to take a bolder step.

The other path we could call the socio-environmental approach. The airlines have made a passing attempt at this by turning the cabin lights down on red-eye flights. I recently wrote about the “exposome,” which some investigators define as the total non-genetic exposures an individual endures during a lifetime and which in many situations has a negative effect on the individual’s health. These two papers clearly demonstrate that noise and nighttime artificial light are potent features of an uncountable number of individuals’ exposomes.

Noise and artificial light are both things that as a society we have the power to control if we could only muster up the political will to do so. Unfortunately, it is going to require something far beyond these two relatively obscure studies to move the needle in the direction of a healthier population. It’s is not a stretch to put obesity and the attention deficit phenomenon under this same umbrella where our society needs to look at itself for the answers.

 

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

They’re literally not better. Idealistically, sure, but literally not. And there’s really no debate. Meaning there’s never been a reproducible diet and exercise intervention that has led to anywhere near the average weight lost by those taking obesity medications. Furthermore, when it comes to the durability of weight lost, the gulf between outcomes with diet and exercise vs obesity medications is even more dramatic.

Looking to the literature, one of the most trotted out studies on lifestyle’s impact on weight over time is the Look AHEAD trial. Before useful obesity medications came on the scene, I trotted it out myself. Why? Because it was heartening when faced with the societal refrain that diet and exercise never worked to be able to show that yes, in fact they do. But how well?

Looking to Look AHEAD’s 4-year data (Obesity [Silver Spring]. 2011 Oct;19[10]:1987-1998), those randomized to the intensive lifestyle initiative arm averaged a 4.7% total body weight loss – an amount that remained the same at 8 years. But I chose 4 years because that’s a better comparison with the semaglutide SELECT trial that revealed at 4 years, the average sustained weight lost was more than double that of Look AHEAD’s, at 10.2%. Meanwhile the recently released SURMOUNT-4 study on tirzepatide reported that at 88 weeks, the average weight lost by participants was a near bariatric surgery level of 25.3% with no signs suggestive of pending regains.

Now maybe you want to cling to the notion that if you just try hard enough, your diet and exercise regime can beat our new meds. Well, it’s difficult to think of a more miserable, often actual vomit-inducing intervention, than the spectacle that used to air weekly on prime time called The Biggest Loser, where participants lived on a ranch and were berated and exercised all day long for the chance to lose the most and win a quarter of a million dollars. But even there, the meds prove to be superior. Although the short-term Biggest Loser data do look markedly better than meds (and than bariatric surgery), whereby the average participant lost 48.8% of their body weight during the grueling 7-month long, 24/7 competition, by postcompetition year 6, the average weight lost dropped to 12.7%.

Yet on November 26, when word came out that Medicare is likely to extend coverage to obesity medications for far more Americans, one of the most common refrains was something along the lines of yes, lifestyle modification is the best choice for dealing with obesity but it’s good that there will be medication options for those where that’s insufficient.

What?

The only reason that the world isn’t comfortable with the eminently provable truth that diet and exercise are inferior to obesity medications for weight management is weight bias. The message is that people simply aren’t trying hard enough. This despite our comfort in knowing that medications have more of an impact than lifestyle on pretty much every other chronic disease. Nor can I recall any other circumstance when coverage of a remarkably effective drug was qualified by the suggestion that known-to-be-inferior interventions are still the best or favored choice.

At this point, obesity medications are plainly the first-line choice of treatment. They provide not only dramatically greater and more durable weight loss than lifestyle interventions, they have also been shown to very significantly reduce the risk for an ever-growing list of other medical concerns including heart attacks, strokes, type 2 diabetes, hypertension, sleep apnea, fatty liver disease, and more, while carrying minimal risk.

Let it also be said that improvements to diet and exercise are worth striving for at any weight, though one should not lose sight of the fact that perpetual, dramatic, intentional, behavior change in the name of health requires vast amounts of wide-ranging privilege to enact — amounts far beyond the average person’s abilities or physiologies (as demonstrated with obesity by decades of disappointing long-term lifestyle outcome data). 

Let it also be said that some people will indeed find success solely through lifestyle and that not every person who meets the medical criteria for any medication’s prescription, including obesity medications, is required or encouraged to take it. The clinician’s job, however, at its most basic, is to inform patients who meet medical use criteria of their options, and if a medication is indicated, to inform them of that medication’s risks and benefits and expected outcomes, to help their patients come to their own treatment decisions.

It’s not a bad thing that we have medications that deliver better outcomes than lifestyle — in fact, it’s terrific, and thankfully that they do is true for pretty much every medical condition for which we have medication. That’s in fact why we have medications! And so this constant refrain of golly-gee wouldn’t it be better if we could just manage obesity with lifestyle changes needs to be put to rest — we literally know it wouldn’t be better, and it’s only weight bias that would lead this evidence-based statement to seem off-putting.

Dr. Freedhoff is Associate Professor, Department of Family Medicine, University of Ottawa, and Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada. He reported conflicts of interest with the Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

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

The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

The results of the SUMMIT trial of the long-acting agonist of glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors, tirzepatide, in patients with heart failure with preserved ejection fraction (HFpEF) and obesity are positive. But the trial design leaves clinicians and regulators with big doses of uncertainty.

Known Facts About HFpEF

HFpEF has exceeded heart failure with reduced ejection fraction (HFrEF) as the most common form of heart failure. HFpEF differs from HFrEF in that patients with preserved ejection fraction often present later in life with more comorbidities.

Some of these comorbidities are on the causal pathway of heart failure. Obesity, for instance, both associates with HFpEF and surely causes the diastolic dysfunction central to the condition. This may be a direct effect via high excess adipose tissue or an indirect effect via pro-inflammatory pathways.

GLP-1 agonists and the dual-acting GIP/GLP1 agonist tirzepatide have proven efficacy for weight loss. Semaglutide has previously been shown to improve quality of life and physical functioning in two small trials of patients with HFpEF and obesity. Semaglutide also reduced hard clinical outcomes in patients with obesity and these other conditions: chronic kidney disease, diabetes, and established atherosclerotic vascular disease.

This class of drugs is costly. The combination of both high drug costs and highly prevalent conditions such as obesity and HFpEF forces clinicians to make both value and clinical judgments when translating evidence.

 

The SUMMIT Trial

The SUMMIT trial aimed to evaluate tirzepatide’s effect on typical heart failure events, health status and functional capacity in patients with obesity and HFpEF. A total of 731 patients were randomly assigned to receive to tirzepatide or placebo.

Investigators chose two co-primary endpoints. The first was a composite of cardiovascular (CV) death and worsening heart failure events—the latter could be a hospitalization for heart failure, a visit for intravenous diuretics, or intensification of oral diuretics. The idea behind this rather unique composite was to capture all heart failure events. The second co-primary endpoint was a change in baseline Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS) at 1 year.

Characteristics of the patients included an average age of 65 years, 55% were female, the average body mass index was 38, and the mean left ventricular ejection fraction was 61% (the minimum for trial entry was 50%). Just under half had been hospitalized for heart failure in the year before trial entry.

 

Tirzepatide Results

The primary outcome of CV death and first heart failure event occurred in 36 patients (9.9%) in the tirzepatide group and 56 patients (15.3%) in the placebo group, for a hazard ratio of 0.62 (95% CI, 0.41-0.95; P =.026).

The 5.4% absolute risk reduction in the primary endpoint was completely driven by lower rates of heart failure events (8% vs 14.2%). CV death was actually higher in the tirzepatide arm, but the number of deaths was low in both arms (8 vs 5).

The rate of hospitalizations due to heart failure was lower with tirzepatide (3.3% vs 7.1%), as was intensification of oral diuretics (4.7% vs 5.7%).

The second co-primary endpoint of change from baseline in KCCQ-CSS favored tirzepatide.

Other secondary endpoints also favored tirzepatide: longer 6-minute walk distance, greater change in body weight (-11.6%), and lower high-sensitivity C-reactive protein levels and systolic blood pressure (-4.7 mm Hg).

 

Authors’ Conclusions and Expert Comments

At the American Heart Association Scientific Sessions, the primary investigator Milton Packer, MD, said SUMMIT was the first trial of patients with obesity and HFpEF that had major heart failure outcomes as the primary endpoint. And that tirzepatide changed the clinical trajectory of the disease.

Jennifer Ho, MD, associate professor of medicine at Harvard Medical School, Boston, Massachusetts, said, “This really is a practice-changing trial and cements this type of therapy as one of the cornerstones of obesity and HFpEF treatment.”

Other experts cited a recently published pooled analysis of semaglutide trials looking specifically at patients with HFpEF and found lower rates of HF events with the GLP-1 agonist.

The SUMMIT trial results were covered in 53 news outlets— nearly all with glowing headlines.

 

My Six Concerns With SUMMIT

The trial delivered statistically positive findings. What’s more, patients lost weight, and a greater than 11% weight loss difference is meaningful. Patients with a baseline weight of more than 100 kg who lose this much weight are bound to feel and function better.

The first problem comes when we ask whether the results are disease-modifying. There was no difference in CV death. And the number of hospitalizations for heart failure — the more standard endpoint — was low, at only 12 and 26, respectively. Contrast this with the DELIVER trial of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in HFpEF where there were nearly 750 hospitalizations for heart failure and PARAGON-HF of sacubitril-valsartan vs valsartan in HFpEF, where there were nearly 1500. SUMMIT simply had too few events to make conclusions — a point Packer has made regarding AF ablation trials in patients with heart failure.

I have previously called GLP-1 drugs disease-modifying in patients with obesity and atherosclerotic disease. This is because the SELECT trial of semaglutide randomized more than 17,000 patients and recorded a 20% reduction in hard outcomes. And there were more than 1200 primary outcome events. SUMMIT does not come close to this measure.

The second issue is short follow-up. These were 65-year-old patients and with only 2 years of follow-up, it is hard to make conclusions regarding whether or not these drugs can provide long-term benefit.

The third issue is that SUMMIT authors don’t tell us the number of all-cause hospitalizations. I was part of a recently published meta-analysis of more than 100 heart failure trials that raised questions regarding the value of hospitalizations for heart failure as a surrogate for heart failure outcomes.

For instance, we found that in large trials there was great variability in the ability of a reduction in HF hospitalizations to predict a reduction in all-cause hospitalization. In small trials, such as SUMMIT, it would likely be impossible to predict how the reduction in HF hospitalization would predict all-cause hospitalization. I believe all-cause hospitalization is a more inclusive endpoint because it is bias free; it captures benefits and potential harms of the therapy; and it is patient-centered, because patients probably do not care what type of hospitalization they avoid.

The fourth issue with SUMMIT is the difficulty in maintaining blinding, which reduces confidence in outcomes that require clinical decisions or patient judgments. Owing to gastrointestinal symptoms, decreased appetite, and weight loss, patients on this class of drugs are very likely to know their treatment assignment. This is a criticism of not only SUMMIT but all GLP-1 agonist trials. The fact that blinding is difficult to maintain argues for choosing endpoints less susceptible to bias, such as CV death or all-cause hospitalization.

Proponents of tirzepatide for this indication might argue that unblinding is less of an issue because of objective endpoints such as biomarkers. And they have a point, but nearly all other endpoints, especially the co-primary endpoint of KCCQ-CSS, are largely susceptible to bias.

The fifth and main problem comes in translating this evidence in the clinic. Should doctors give up on nondrug means of weight loss? All of the positive outcome trials in this class of drugs have also shown weight loss. I believe we should take these data and use them to re-invigorate our advocacy for weight loss without medication. I know the standard answer to this proposal is nihilism: It just will not work. And I cannot deny that we have failed previously in our efforts to help patients lose weight. But perhaps now, with the vast amount of data, we can be more persuasive. Imagine a world where key opinion leaders made weight loss the message rather than prescription of a drug.

Finally, if you approach SUMMIT from the view of a regulator, with its small numbers of outcome events and bias-susceptible endpoints, you cannot allow a disease-modifying claim. For that we would need a properly powered trial that shows that the drug reduces both CV death and all-cause hospitalization.

In the end, SUMMIT is not close to changing treatment norms in patients with HFpEF. As evidence-based clinicians, we should demand more from our partners in industry and academia.

Dr. Mandrola practices cardiac electrophysiology in Baptist Medical Associates, Louisville, Kentucky, and is a writer and podcaster for Medscape. He espouses a conservative approach to medical practice. He participates in clinical research and writes often about the state of medical evidence. He has disclosed no relevant financial relationships.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.

Three basic truths about ultraprocessed foods: Junk food, available pretty much everywhere, tastes great. Advertising works. And most of us don’t crave green leafy salads when we’re hungry.

Of those three truths, the one that tends to get more public health attention is advertising. More specifically, advertising junk food to kids. 

Back in the days when cable television was king of all free time, study after study tried to quantify junk- and fast-food advertising to kids and speculated about its impact on childhood obesity rates. But as broadcast television use began fading, advertisers — and, of course, studies about advertising — turned their attention first to gaming and now to social media.

The social media numbers are quite staggering. According to a study published — probably not coincidentally — on Halloween, looking at the 40 top brands of junk- and fast food sold in Canada, those 40 brands alone were mentioned over 16 million times by social media users, reaching an estimated 42 billion total users within a 1-year period. 

And unique to the challenge of junk- and fast-food advertising on social media is that it also includes “earned” advertising, the kind not paid for by manufacturers but rather the kind where friends, family, and influencers post about junk food. Occasionally, though, these lines are blurred by initiatives from fast-food manufacturers explicitly encouraging social sharing. Consequently, even were there a desire, there isn’t likely to be a regulatory mechanism to markedly reduce it. 

For years, here in North America, excepting Quebec, the desire has been mainly to just talk about how concerned we are about junk-food advertising to kids. Elsewhere, however, some countries tried to do more, including both Mexico and Chile, which put kid-targeted TV food advertising bans in place in 2014 and 2016, respectively. 

Did they work? It depends on what outcome you’re considering. If the question is, did they work in regard to obesity? — which is how everyone tends to frame the question — by themselves, probably not. No one sandbag stops a flood, and though junk-food advertising is certainly a sandbag, we’re still facing a torrential downpour of obesity contributors. No doubt they did work to reduce kids’ exposure to junk-food advertising on television, but what remains to be seen is whether there is a means to now tackle social media’s generous servings of the same. Moreover, the obesity lens is the wrong one. Ultraprocessed food consumption isn’t good for anyone, regardless of weight, and its reduced marketing and consumption is a worthy goal of its own.

But Chile and Mexico are filling more than single sandbags, as both countries have rolled out a suite of interventions they are hoping will help improve nutrition: from front-of–package labeling reforms and warnings, to the banning of advertising geared specifically to appeal to children (like sugary cereal cartoon mascots), to implementing sugar-sweetened-beverage taxes, to having blanket overall bans on food advertising during the daytime.

Mexico is even taking first steps to start addressing junk food’s ubiquity by banning its sale in schools altogether. Schools found to be selling common Mexican junk food fare, such as sugary fruit drinks; chips; artificial pork rinds; and soy-encased, salty peanuts with chili, will see their administrators facing heavy fines. 

Because therein lies the biggest rub. Going back to those three simple truths, junk food is hyperpalatable and consequently tends to be what we crave when we’re hungry. So even if we miraculously one day do more than just talk about advertising reforms, and especially given that we won’t be able to do anything about social media’s earned product placements, junk food’s ubiquitous availability within arms’ reach or on our Uber Eats apps will see us be likely to continue its excessive consumption. 

That’s not to say we shouldn’t emulate Mexico and Chile’s initiatives, nor that they shouldn’t continue to build upon them, but one thing is certain: Human nature and inconvenient truths around food are incredibly powerful forces that we haven’t yet figured out how to tame.

Dr. Freedhoff, Associate Professor, Department of Family Medicine, University of Ottawa; Medical Director, Bariatric Medical Institute, Ottawa, Ontario, Canada, has disclosed relevant financial relationships with Bariatric Medical Institute, Constant Health, Novo Nordisk, and Weighty Matters.

A version of this article appeared on Medscape.com.