Obesity

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

TOPLINE:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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 appeared on Medscape.com.

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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 appeared on Medscape.com.

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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 appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

TOPLINE:

VIENNA, AUSTRIA — Participants with type 2 diabetes who were able to stop insulin for up to 12 months after receiving the novel recellularization via electroporation therapy (ReCET) procedure in combination with treatment with semaglutide maintained their response at 24 months.

METHODOLOGY:

• ReCET technology, manufactured by Endogenex, uses a specialized catheter that ablates the duodenal mucosa with electroporation, enhancing sensitivity to endogenous insulin.
• In the first-in-human study, a total of 14 participants (aged 28-75 years; body mass index, 24-40) underwent the ReCET procedure. They then followed a 2-week isocaloric liquid diet, after which they were initiated on semaglutide and gradually titrated up to 1 mg/wk.
• Patients were followed for a total of 24 months.

TAKEAWAY:

• Of the 14 participants, 12 (86%) no longer required insulin at the 6- and 12-month follow-ups.
• At the 24-month follow-up, 11 patients were still insulin-free while maintaining A1c levels below 7.5%. (One patient withdrew consent at 18 months.)
• Semaglutide at the maximum dose was well-tolerated by 93% of participants. One patient experienced nausea that limited titration to the maximum dose. There were no serious adverse events to the ReCET procedure.
• Researchers have started the EMINENT-2 trial that will compare the use of ReCET with a sham procedure. All patients will still receive semaglutide.

IN PRACTICE:

• “These findings are very encouraging, suggesting that ReCET is a safe and feasible procedure that, when combined with semaglutide, can effectively eliminate the need for insulin therapy,” said the study’s lead author.
• It’s a novel way of treating type 2 diabetes using a single endoscopic procedure instead of repeated insulin injections, Busch explained. “But we do need to consider whether repeat treatment will be necessary because I don’t believe this will be forever.”

SOURCE:

This study was led by Celine Busch, MBBS, a PhD candidate in gastroenterology at Amsterdam University Medical Center, Amsterdam, the Netherlands, and was presented (abstract OP049) at the United European Gastroenterology (UEG) Week 2024 in Vienna, Austria, on October 14, 2024.

LIMITATIONS:

Limitations included the small sample size, uncontrolled nature, and bias due to combination therapy.

DISCLOSURES:

This study received an unrestricted research grant from Endogenex. No other relevant disclosures were declared.

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

TOPLINE:

Eating more eggs is linked to weight gain in postmenopausal women, especially those with a high intake of Western foods such as processed and red meat, French fries, sweets, and deserts. Genetic predisposition for a high body mass index (BMI) also influences weight gain with higher egg intake.

METHODOLOGY:

• Egg consumption and elevated body weight are each linked to an increased risk for serious chronic diseases; however, whether elevated body weight mediates the association between egg intake and an elevated risk for serious chronic diseases needs further assessment.
• To investigate the association between eating eggs and weight gain, as well as the role of genetic susceptibility to an elevated BMI, researchers conducted a prospective study including 4439 postmenopausal women of European descent from the Women’s Health Initiative (WHI).
• They measured the participants’ consumption of egg and egg nutrients using a self-administered food frequency questionnaire.
• Changes in the consumption of eggs and egg nutrients such as cholesterol, choline, and betaine were assessed between baseline and follow-up visits at 1, 3, 6, and 9 years.
• The primary outcome was the change in body weight between baseline and each follow-up visit. Furthermore, an exploratory analysis evaluated how eating Western foods and genetic predisposition for a high BMI (assessed through a polygenic score) influenced weight change.

TAKEAWAY:

• An increased consumption of eggs was associated with weight gain, showing a positive linear trend at 1, 2, 3, and 6 years. By the third year, women whose egg consumption had increased by two eggs per week gained 0.70 kg more weight (P = .0002) than women whose egg consumption was reduced by 2.4 eggs per week (P-linear < .0001).
• An increase in the consumption of nutrients obtained from eggs, including cholesterol (P-linear < .0001) and choline (P-linear < .02), was positively associated with weight gain.
• Women with a higher consumption of Western foods showed significant associations between changes in egg, cholesterol, and choline intake and weight gain.
• A significant association was found between the BMI polygenic score and changes in body weight, with women most genetically predisposed to a higher BMI showing greater weight gain when their egg consumption increased by an average of 3.5 eggs per week.

IN PRACTICE:

“These results suggest that even relatively small increases or decreases in egg consumption could cause increases or decreases, respectively, in body weight among postmenopausal women, unless there are adequate compensating changes in factors such as dietary energy intake or physical activity,” the authors wrote. “Our results require confirmation,” they added.

SOURCE:

This study, led by James A. Greenberg, Department of Health and Nutrition Sciences, Brooklyn College, The City University of New York, was published online in Clinical Nutrition.

LIMITATIONS: 

This observational study was susceptible to residual confounding, which suggests that the observed associations may not have established causality. Additionally, the results were according to data from a group of postmenopausal American women of European descent, which limited the generalizability to other populations.

DISCLOSURES:

The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health & Human Services. The authors declared no conflicts of interest.

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

TOPLINE:

Eating more eggs is linked to weight gain in postmenopausal women, especially those with a high intake of Western foods such as processed and red meat, French fries, sweets, and deserts. Genetic predisposition for a high body mass index (BMI) also influences weight gain with higher egg intake.

METHODOLOGY:

• Egg consumption and elevated body weight are each linked to an increased risk for serious chronic diseases; however, whether elevated body weight mediates the association between egg intake and an elevated risk for serious chronic diseases needs further assessment.
• To investigate the association between eating eggs and weight gain, as well as the role of genetic susceptibility to an elevated BMI, researchers conducted a prospective study including 4439 postmenopausal women of European descent from the Women’s Health Initiative (WHI).
• They measured the participants’ consumption of egg and egg nutrients using a self-administered food frequency questionnaire.
• Changes in the consumption of eggs and egg nutrients such as cholesterol, choline, and betaine were assessed between baseline and follow-up visits at 1, 3, 6, and 9 years.
• The primary outcome was the change in body weight between baseline and each follow-up visit. Furthermore, an exploratory analysis evaluated how eating Western foods and genetic predisposition for a high BMI (assessed through a polygenic score) influenced weight change.

TAKEAWAY:

• An increased consumption of eggs was associated with weight gain, showing a positive linear trend at 1, 2, 3, and 6 years. By the third year, women whose egg consumption had increased by two eggs per week gained 0.70 kg more weight (P = .0002) than women whose egg consumption was reduced by 2.4 eggs per week (P-linear < .0001).
• An increase in the consumption of nutrients obtained from eggs, including cholesterol (P-linear < .0001) and choline (P-linear < .02), was positively associated with weight gain.
• Women with a higher consumption of Western foods showed significant associations between changes in egg, cholesterol, and choline intake and weight gain.
• A significant association was found between the BMI polygenic score and changes in body weight, with women most genetically predisposed to a higher BMI showing greater weight gain when their egg consumption increased by an average of 3.5 eggs per week.

IN PRACTICE:

“These results suggest that even relatively small increases or decreases in egg consumption could cause increases or decreases, respectively, in body weight among postmenopausal women, unless there are adequate compensating changes in factors such as dietary energy intake or physical activity,” the authors wrote. “Our results require confirmation,” they added.

SOURCE:

This study, led by James A. Greenberg, Department of Health and Nutrition Sciences, Brooklyn College, The City University of New York, was published online in Clinical Nutrition.

LIMITATIONS: 

This observational study was susceptible to residual confounding, which suggests that the observed associations may not have established causality. Additionally, the results were according to data from a group of postmenopausal American women of European descent, which limited the generalizability to other populations.

DISCLOSURES:

The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health & Human Services. The authors declared no conflicts of interest.

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

TOPLINE:

Eating more eggs is linked to weight gain in postmenopausal women, especially those with a high intake of Western foods such as processed and red meat, French fries, sweets, and deserts. Genetic predisposition for a high body mass index (BMI) also influences weight gain with higher egg intake.

METHODOLOGY:

• Egg consumption and elevated body weight are each linked to an increased risk for serious chronic diseases; however, whether elevated body weight mediates the association between egg intake and an elevated risk for serious chronic diseases needs further assessment.
• To investigate the association between eating eggs and weight gain, as well as the role of genetic susceptibility to an elevated BMI, researchers conducted a prospective study including 4439 postmenopausal women of European descent from the Women’s Health Initiative (WHI).
• They measured the participants’ consumption of egg and egg nutrients using a self-administered food frequency questionnaire.
• Changes in the consumption of eggs and egg nutrients such as cholesterol, choline, and betaine were assessed between baseline and follow-up visits at 1, 3, 6, and 9 years.
• The primary outcome was the change in body weight between baseline and each follow-up visit. Furthermore, an exploratory analysis evaluated how eating Western foods and genetic predisposition for a high BMI (assessed through a polygenic score) influenced weight change.

TAKEAWAY:

• An increased consumption of eggs was associated with weight gain, showing a positive linear trend at 1, 2, 3, and 6 years. By the third year, women whose egg consumption had increased by two eggs per week gained 0.70 kg more weight (P = .0002) than women whose egg consumption was reduced by 2.4 eggs per week (P-linear < .0001).
• An increase in the consumption of nutrients obtained from eggs, including cholesterol (P-linear < .0001) and choline (P-linear < .02), was positively associated with weight gain.
• Women with a higher consumption of Western foods showed significant associations between changes in egg, cholesterol, and choline intake and weight gain.
• A significant association was found between the BMI polygenic score and changes in body weight, with women most genetically predisposed to a higher BMI showing greater weight gain when their egg consumption increased by an average of 3.5 eggs per week.

IN PRACTICE:

“These results suggest that even relatively small increases or decreases in egg consumption could cause increases or decreases, respectively, in body weight among postmenopausal women, unless there are adequate compensating changes in factors such as dietary energy intake or physical activity,” the authors wrote. “Our results require confirmation,” they added.

SOURCE:

This study, led by James A. Greenberg, Department of Health and Nutrition Sciences, Brooklyn College, The City University of New York, was published online in Clinical Nutrition.

LIMITATIONS: 

This observational study was susceptible to residual confounding, which suggests that the observed associations may not have established causality. Additionally, the results were according to data from a group of postmenopausal American women of European descent, which limited the generalizability to other populations.

DISCLOSURES:

The WHI program was funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health & Human Services. The authors declared no conflicts of interest.

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