Obesity Medications Work Best for Young People When Combined With Lifestyle Support
Key Takeaways:
- Among young people with obesity, pairing medication with structured behavioural and lifestyle support produced the largest short-term reductions in BMI.
- Metformin combined with behaviour and lifestyle treatment lowered BMI by 4.95, whereas metformin used on its own showed no significant change.
- Semaglutide plus counselling was linked to the biggest BMI reduction of any approach, although this estimate rested on a single trial.
Support matters as much as the medicine
Children and adolescents with obesity who received a combination of medication and structured lifestyle treatments achieved the greatest short-term reductions in BMI, according to a new evidence synthesis. The findings point away from prescribing in isolation and towards a model in which medication is layered on top of behavioural and family support rather than used as a stand-alone fix.
How the study was conducted
Researchers carried out a systematic review and network meta-analysis, searching the literature databases through June 2025, to work out which obesity treatments perform best for young people. A network meta-analysis allows multiple interventions to be compared against one another even where they have not all been tested head-to-head in the same trial.
The final analysis brought together 42 randomised clinical trials involving 3835 participants aged 10–19 years with obesity. The median age was 14.5 years, and 59.2% of participants were female individuals. Most of the included studies followed up participants over 6–12 months, placing the emphasis firmly on short-term outcomes.
The interventions assessed fell into several categories: structured behavioural and lifestyle treatments, in both standard and intensive forms; counselling; medications, including GLP-1 receptor agonists, metformin, orlistat, and phentermine–topiramate; and combinations of medication with lifestyle treatment.
The primary outcomes were changes in BMI and BMI z-score, while the secondary outcomes were changes in waist circumference, fat mass, and lean mass. The interventions were then ranked in order of effectiveness.
On study quality, the risk for bias was judged low in 21.4% of trials and high in 26.2%, with the remaining 52.4% raising some concerns. The overall certainty of the evidence ranged from very low to high, so the strength of the findings varies considerably from one comparison to another.
What the analysis found
Across the 35 trials that reported BMI and the 19 that reported BMI z-score, medications produced larger reductions when paired with lifestyle treatments than when used alone. Metformin illustrates the pattern clearly: combined with behaviour and lifestyle treatment it was associated with a reduction of 4.95 in BMI, whereas metformin used on its own showed no significant change in BMI.
Semaglutide plus counselling was associated with the largest reduction in BMI (mean difference [MD], −8.31) and in BMI z-score (MD, −1.80). This estimate, however, came from a single trial, so it should be read with caution.
Behavioural and lifestyle treatment on its own was associated with reductions in BMI (MD, −3.85; five studies) and in BMI z-score (MD, −0.89; one study) – results that matched or exceeded the effect of certain medications used alone. Combination treatments were linked to the largest reductions in fat mass, drawing on 21 studies.
What it means in practice
The authors framed the combined approach as consistently outperforming medication given without support. “[The] finding suggests that even combining medication with basic counselling was still superior to giving medication without any lifestyle support,” the researchers wrote. “Medications should never be prescribed in isolation; a person-centered, family-centered approach matching treatment intensity to medical need is essential,” they added.
Where the research came from
The study was led by Ke-wen Wan, MSc, of Hong Kong Baptist University in Hong Kong SAR, China. It was published online on 22 June in JAMA Pediatrics.
Limitations to consider
Several caveats temper the results. The findings for newer medications were based on only a few small trials, which limits confidence in those specific estimates. The wide age range may have obscured differences by age or stage of puberty, since a 10-year-old and a 19-year-old can respond very differently to the same intervention. Most of the trials also did not report data on race, ethnicity, or income, leaving open questions about how the findings apply across different populations.
Funding and disclosures
The study received funding from grants from Hong Kong Baptist University. One author reported serving on professional boards related to childhood obesity and receiving travel grants or reimbursements, and another author reported receiving consulting fees from pharmaceutical companies. Detailed disclosures are available in the original article.
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GLP-1 Medicines for Weight Loss Reach Record Use Among US Adults
Key Takeaways:
- Eleven per cent of US adults report currently taking GLP-1 medicines for weight loss in 2026, a substantial rise from three per cent in 2024.
- Awareness of GLP-1 medicines intended for weight loss has increased to 91 per cent, while the US adult obesity rate has declined from its 2022 peak of 39.9 per cent to 36.4 per cent so far in 2026.
- Brand-name GLP-1 medicines remain the most commonly used option, but cost and insurance coverage appear to be driving some people towards compounded or custom-mixed versions.
GLP-1 use for weight loss continues to rise
The proportion of US adults who say they are currently taking GLP-1 medicines for weight loss has reached a new high in 2026, according to data from the Gallup National Health and Well-Being Index.
Eleven per cent of US adults now report current use of these medicines for weight loss purposes. This represents a significant increase from 2024, when three per cent reported current use. Lifetime use has also risen, with 15 per cent of US adults saying they have taken a GLP-1 medicine for weight loss at some point. This is an increase of nine percentage points.
The findings are based on a web survey of 5,065 US adults conducted between 28 May and 5 June 2026. The survey used the probability-based Gallup Panel, which includes respondents from all 50 US states and the District of Columbia.
How Gallup measured GLP-1 use
To assess whether people had ever used GLP-1 medicines for weight loss, Gallup asked respondents:
“Have you ever taken weight loss medications such as semaglutide (brand names Ozempic and Wegovy), liraglutide (brand name Saxenda) or tirzepatide (brand names Mounjaro and Zepbound)?”
People who answered “yes” were then asked a follow-up question to determine whether they were currently taking one of these medicines:
“Are you currently taking weight loss medications such as semaglutide (brand names Ozempic and Wegovy), liraglutide (brand name Saxenda) or tirzepatide (brand names Mounjaro and Zepbound)?”
These questions allowed Gallup to distinguish between lifetime use and current use among US adults.
FDA approvals have expanded the market
The rise in GLP-1 use follows the approval of several medicines for weight loss in the US. The Food and Drug Administration approved Novo Nordisk’s Wegovy, which contains semaglutide, for weight loss in 2021.
Since then, additional options have become available. Eli Lilly’s Zepbound, which contains tirzepatide, received FDA approval in November 2023.
As more treatment options have entered the market, public awareness has also increased. Gallup reports that 91 per cent of Americans are now aware of GLP-1 medicines intended for weight loss, up from 80 per cent in 2024.
Adult obesity has declined from its 2022 peak
Gallup’s latest findings show that the US adult obesity rate has continued to fall after reaching a record high of 39.9 per cent in 2022. So far in 2026, the adult obesity rate stands at 36.4 per cent.
Gallup describes this as a statistically meaningful decline. The trend has continued to move in the opposite direction to national GLP-1 use, which has increased over the same period.
Gallup calculates obesity using the federal standard of a body mass index of 30 or higher. BMI is calculated using respondents’ self-reported height and weight.
The organisation notes that self-reported data may produce somewhat lower estimates than studies based on randomised clinical measurements of height and weight. Gallup suggests that a “vanity effect” in how people report their own height and weight may help explain this difference. However, because Gallup has used a consistent method over time, the data still provides useful information about changes in the adult obesity rate.
Diabetes diagnoses have levelled off
While obesity levels have declined, the proportion of US adults who report having been diagnosed with diabetes has remained steady since 2023. This follows 15 years of gradual increases that occurred alongside rising obesity rates.
Gallup notes that a falling obesity rate would be expected to stabilise, but not necessarily reduce, the proportion of adults who have ever been diagnosed with diabetes. Diabetes is described in the original analysis as a lifelong disease that can be managed but not cured.
To measure diabetes prevalence, Gallup asked US adults:
“Has a doctor or nurse ever told you that you have diabetes?”
The diabetes rate includes people with Type 1 diabetes and people with Type 2 diabetes. The 2026 figures for obesity and diabetes are based on 10,091 respondents from surveys conducted from 18 February to 3 March and from 28 May to 5 June 2026.
Brand-name GLP-1 medicines remain the most common option
Among adults currently taking GLP-1 medicines for weight loss, brand-name options remain the most common.
Gallup found that 68 per cent of current use involves brand-name GLP-1 medicines such as Ozempic or Wegovy. By comparison, 19 per cent of current use involves compounded or custom-mixed versions of the medicine.
A further 12 per cent of people currently taking a GLP-1 medicine for weight loss are unsure whether they are using a brand-name medicine.
People using compounded versions report slightly higher effectiveness
Gallup also compared perceived effectiveness between people taking brand-name GLP-1 medicines and those taking compounded or custom-mixed versions.
People using compounded or custom-mixed GLP-1 medicines were slightly more likely to describe the medicine as “extremely effective”. Thirty-nine per cent of people in this group gave that response, compared with 32 per cent of people using brand-name GLP-1 medicines.
However, both groups generally regarded the medicines as effective. Seventy-seven per cent of people using compounded or custom-mixed versions said the medicine was either “effective” or “extremely effective”. Among people using brand-name GLP-1 medicines, the figure was 74 per cent.
Some people are switching from brand-name to compounded GLP-1 medicines
Although brand-name medicines continue to account for most current GLP-1 use, Gallup’s findings suggest that compounded or custom-mixed versions are gaining ground.
Among people currently using compounded or custom-mixed GLP-1 medicines, 35 per cent report having switched from a brand-name medicine. By contrast, 10 per cent of people currently using brand-name GLP-1 medicines say they switched from a compounded or custom-mixed version.
This suggests that movement towards compounded or custom-mixed GLP-1 medicines is greater than movement in the opposite direction.
Cost and insurance coverage appear to be major factors in this shift. Among people who switched from a brand-name GLP-1 medicine to a compounded version, 66 per cent cited cost or insurance coverage as their main reason for switching. Among those who switched from a compounded version to a brand-name medicine, 34 per cent cited cost or insurance coverage as the primary reason.
Wider implications for obesity and diabetes trends
The growing use of GLP-1 medicines for weight loss may point to broader health implications for adults in the US. Gallup’s analysis indicates that increased use of these medicines has coincided with a decline in the adult obesity rate and a levelling off in diabetes diagnoses after years of increases.
Previous research cited in the original analysis has shown a general alignment between GLP-1 use and declining obesity rates across age groups. One exception is adults aged 65 and older, among whom the reported effectiveness of GLP-1 medicines is lower.
Brand-name GLP-1 medicines still lead the market by a wide margin. However, the lower cost of compounded or custom-mixed versions appears to be contributing to a shift away from brand-name options for some people. This may be expanding access to GLP-1 medicines across broader sections of the population, although access remains limited.
Gallup suggests that this broader availability may be one factor helping to drive overall GLP-1 use higher in the US.
Source: Gallup
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Many Who Stop GLP-1 Medications Restart Within a Year, Study Finds
Key Takeaways:
- Around 4 in 10 people with type 2 diabetes stopped their GLP-1 medication within the first year, rising to nearly 6 in 10 by the end of two years.
- Of those who stopped, more than half restarted within a year and nearly two-thirds within two years, suggesting use is often start-and-stop rather than permanent.
- Newer medications, a prescription from an endocrinologist, and fewer stomach-related side effects were all linked to a lower likelihood of stopping.
Use is more start-and-stop than assumed
People prescribed GLP-1 medications are more likely to start and stop treatment than many assume, according to a study being presented on Sunday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
“Our study asked two questions that haven’t been well answered until now: How many people with type 2 diabetes taking GLP-1 medications actually stop using them? And how many restart them?” said Sainikhil Sontha, M.S., a research associate at Boston University School of Public Health in Boston, Massachusetts.
How the study was carried out
The researchers ran a retrospective cohort study using Komodo Health US claims data covering January 2019 to June 2025. The group included adults aged 18 to 64 years with a BMI of 25 kg/m² or above and type 2 diabetes who had started liraglutide, semaglutide, or tirzepatide, and who had previously enrolled within the last year with more than six months of follow-up.
Discontinuation was defined as a gap of more than 60 days in filling a GLP-1 prescription. Obtaining a new fill after discontinuation was counted as reinitiation.
How many people stopped
“Using insurance records from more than 60,000 Americans with type 2 diabetes, we found that about 4 in 10 patients stopped their GLP-1 medication within the first year, and nearly 6 in 10 had stopped by the end of two years,” Sontha said.
But the team also found something more encouraging.
How many people restarted
“More than half of those who stopped restarted therapy within a year (41.5%), and nearly two-thirds did so within two years (58%),” Sontha said. “This suggests that for many patients, these medications aren’t being abandoned permanently; use is more start-and-stop than most people assumed.”
Who was more likely to stop
Using Cox proportional hazards models, the researchers also accounted for sociodemographic, clinical, and provider-level predictors.
Sontha and colleagues found that people on Medicaid or Medicare, people who are Black, and those experiencing nausea or other stomach-related side effects (37%) were more likely to discontinue a GLP-1 medication within a year.
What was linked to staying on treatment
People were 10% less likely to stop if their first GLP-1 medication was prescribed by an endocrinologist.
The type of medication also made a difference. People taking newer medications such as tirzepatide were 41% less likely to discontinue than those taking older drugs such as liraglutide, while people taking semaglutide were 28% less likely to discontinue anti-obesity medication use than those on older medications.
Why it matters
“This research matters because consistent use of these medications is what produces their protective effects,” Sontha said. “Stopping early may mean missed opportunities to prevent heart attacks, kidney disease progression and other complications.”
The researchers hope the findings give providers, insurers, and policymakers a clearer picture of which patients need more support to stay on GLP-1 medications.
Source: Endocrine Society
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A Simple Blood Test Could Identify the Most Effective Obesity Medication
Key Takeaways:
- A hypothesis-generating pilot study suggests that fasting blood levels of two incretin hormones – GLP-1 and GIP – may help predict how well people with severe obesity respond to semaglutide and tirzepatide.
- Low fasting GIP was linked to an optimal response to tirzepatide, while low GLP-1 combined with intermediate-to-high GIP was linked to an optimal response to semaglutide.
- The researchers stress that the findings are preliminary and should not guide prescribing until confirmed in larger, adequately powered randomised trials.
A step towards matching patients with the right medication
A straightforward fasting blood test may one day help clinicians decide which obesity medication is most likely to work for an individual patient. That is the tentative conclusion of a new hypothesis-generating pilot study published in the journal Diagnostics, which reports that fasting blood levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) may help predict the therapeutic response to semaglutide and tirzepatide in people living with severe obesity.
Why obesity medications produce different responses
Obesity, characterised by excessive fat accumulation in the body, has become a global epidemic, affecting more than 650 million adults worldwide. The condition is associated with a significantly increased risk of cardiovascular disease, type 2 diabetes, certain cancers, and all-cause mortality.
Among the pharmacological options, glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide, and dual GIP/GLP-1 receptor co-agonists such as tirzepatide, have shown considerable promise in addressing this challenge. One major limitation of these medicines, however, is the marked variability in response between individuals, which has prompted interest in identifying the biological mechanisms that drive this variation.
GLP-1 and GIP are the two principal incretin hormones, secreted by intestinal cells after food is eaten. GLP-1 suppresses appetite and promotes satiety through central nervous system pathways, whereas GIP regulates adipose tissue metabolism and energy expenditure. Acting synergistically, these hormones help to regulate glucose metabolism and appetite, giving them a major role in the management of obesity and type 2 diabetes.
Because the incretin system is frequently dysregulated in obesity, researchers at the University of Catania and MEDISAN, both based in Italy, designed the study to investigate whether fasting blood levels of GLP-1 and GIP could help identify people more likely to respond to semaglutide and tirzepatide.
How the pilot study was designed
The study enrolled 90 adults with a BMI greater than 40 kg/m² (class III obesity). Fasting blood samples were collected to measure each participant’s GLP-1 and GIP levels.
Each hormone was independently divided into low, intermediate, and high tertiles – a statistical division of a dataset into three equal parts – based on its distribution across the study population. Combining the GLP-1 and GIP tertiles produced nine distinct hormone profiles, each containing 10 participants. Within every profile, participants were randomly assigned to receive either semaglutide or tirzepatide, with five people allocated to each medicine per profile.
Response to treatment was assessed at six months. A reduction in body weight of less than 5% was classed as a low response, a reduction of 5–15% as an intermediate response, and a reduction of more than 15% as an optimal response.
Low incretin levels shaped treatment outcomes
The analysis showed that participants in the three profiles characterised by the low GIP tertile achieved an optimal response to tirzepatide, regardless of their GLP-1 levels. This suggests that low fasting GIP was associated with greater responsiveness to exogenous GIP receptor agonists such as tirzepatide.
For semaglutide, participants in two profiles – those characterised by a low GLP-1 tertile combined with an intermediate-to-high GIP tertile – were the only ones to achieve an optimal response. This may indicate that low endogenous GLP-1 availability leaves more GLP-1 receptors free for activation by exogenous semaglutide. The intermediate-to-high levels of endogenous GIP, meanwhile, may point to intact or compensatory incretin secretory capacity that does not interfere with the efficacy of a GLP-1 receptor agonist.
Participants in the profile characterised by high GLP-1 and high GIP tertiles achieved only a low response to both medicines. The authors suggest this may reflect a dysregulated incretin system that was not overcome by pharmacological doses within six months. They note, however, that fasting hormone measurements alone cannot distinguish between incretin secretory deficiency and receptor resistance, making this interpretation speculative.
On the clinical side, participants who achieved an optimal response to either medicine experienced significant reductions in waist circumference and improvements in insulin sensitivity. These changes paralleled the weight-loss patterns observed across the response groups, indicating clinically meaningful improvements in central adiposity and metabolic health.
How receptor occupancy may explain the findings
The observed variation in response may be explained through incretin receptor occupancy. Tirzepatide, as a dual GIP/GLP-1 receptor co-agonist, activates both receptor systems simultaneously. When GIP is present at low abundance (low fasting levels), it cannot fully occupy its receptor, potentially leaving that receptor available for exogenous tirzepatide. Once bound and activated, tirzepatide may then exert greater therapeutic effects by regulating adipose tissue metabolism, energy expenditure, and potentially central appetite regulation.
Semaglutide, which binds and activates the GLP-1 receptor exclusively, may exert its greatest effects when GLP-1 receptors are relatively unoccupied because of low levels of endogenous GLP-1. In these conditions, semaglutide may more effectively restore GLP-1 receptor signalling and deliver its anorectic, insulinotropic, and metabolic effects.
What this could mean for personalised prescribing
Taken together, the study suggests that fasting blood levels of GLP-1 and GIP were associated with the therapeutic response to semaglutide and tirzepatide in people with severe obesity, and may help identify those more likely to respond to treatment. Specifically, low GIP levels were associated with an optimal tirzepatide response, whereas low GLP-1 levels combined with intermediate-to-high GIP levels were associated with an optimal semaglutide response.
Because a single-timepoint measurement of GLP-1 and GIP cannot reveal receptor resistance, the researchers recommend treating these observations as hypothesis-generating, and highlight the need for mechanistic validation through dynamic measurements of incretin levels and receptor activity. Overall, the findings offer preliminary clinical evidence for incretin-guided, personalised pharmacotherapy that could improve treatment outcomes in obesity management.
Limitations and next steps
Several important caveats apply. This was a small, single-centre, open-label pilot study, with only five participants per treatment arm within each hormone profile. In addition, fasting hormone measurements cannot distinguish incretin secretory deficiency from receptor resistance. The authors therefore emphasise that the findings are preliminary and should not guide clinical practice until they are confirmed in larger, adequately powered randomised trials.
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Will Wider Use of GLP-1s Mean Fewer Pills for Older Adults? Yale Study Offers a Reality Check
Key Takeaways:
- Yale researchers found that roughly 15% of polypharmacy cases in adults aged 65 and older – about 3.3 million of 22 million – are attributable to obesity.
- GLP-1 medications are unlikely to meaningfully reduce overall prescription burden in this age group, and their side effects may add further medications.
- From July, eligible Medicare beneficiaries will gain broad access to GLP-1s for obesity treatment under a federally funded demonstration programme running until December 2027.
Rethinking the promise of GLP-1s in geriatric care
As people grow older, they tend to accumulate chronic conditions, many of which require ongoing pharmacological management. While prescription medications play an essential role in disease control, polypharmacy – generally defined as the regular use of five or more drugs – carries a heightened risk of adverse effects, drug–drug interactions, and contraindications. With glucagon-like peptide-1 receptor agonists (GLP-1s) now reshaping obesity care, an open question has emerged: could effectively treating obesity in older adults reduce the number of medications they need overall?
A new study from Yale, published in the Journal of General Internal Medicine, sets out to answer that question by quantifying how much polypharmacy in adults aged 65 and older can be attributed to obesity in the first place.
The theory being tested
The investigators were motivated by a hypothesis that has gained traction in recent years: that better treatment of obesity could cascade into reduced reliance on medications for obesity-related complications such as type 2 diabetes, hypertension, and dyslipidaemia.
“Some in the medical community have theorized that if older adults are treated with GLPs, they can be on fewer medications because we’re treating their obesity and thereby treating other obesity-related conditions,” says Alissa Chen, MD, MPH, instructor of medicine (general medicine) and first author of the study.
To test the assumption, the team examined the extent to which polypharmacy in adults aged 65 and older could be statistically attributed to obesity.
What the study found
The researchers determined that approximately 15% of polypharmacy cases in this population were attributable to obesity. In absolute terms, this represented around 3.3 million of an estimated 22 million cases.
“While that is a lot of patients, there’s certainly a large majority of polypharmacy cases which are not attributable to obesity,” Chen adds.
The implication is significant. Even if GLP-1 therapy proves highly effective at treating obesity and its complications in older adults, the broader medication burden in this age group is driven largely by factors unrelated to body weight. As a result, GLP-1s are unlikely to substantially reduce the total number of prescriptions taken by people aged 65 and over, although they may still meaningfully improve obesity-related health outcomes.
A crossroads for obesity medications in older adults
Research into the use of obesity medications in older adults remains limited, and the long-term implications of widespread GLP-1 prescribing in this population are not yet well understood.
“We’re at a crossroads for the use of obesity medications like GLPs in older adults. This study gives us a first glimpse into one way in which GLPs may change the face of health and healthcare for older adults,” says Alexandra M. Hajduk, PhD, MPH, research scientist (geriatrics) and senior author of the study.
Chen also points out that the side-effect profile of GLP-1 therapy is itself worth considering when projecting medication burden. Common adverse effects, including nausea, acid reflux, and diarrhoea, may prompt the addition of over-the-counter or prescription remedies, potentially offsetting any reductions in other classes of medication.
Expanded medicare access from july
The clinical context is changing rapidly. Starting in July, obesity medications will become available at low cost for eligible Medicare beneficiaries under a federally funded demonstration programme running until December 2027. For the first time, GLP-1 medications will be broadly covered by Medicare for the treatment of obesity.
This expansion is widely expected to drive a surge in GLP-1 prescriptions among older adults. What happens after the demonstration period ends, however, is uncertain. If prices rise sharply once the programme concludes, many people may face the prospect of either paying out of pocket or stopping treatment altogether.
The risks of discontinuation
Stopping GLP-1 therapy is not a neutral event, particularly for older adults whose metabolic health may have improved markedly on treatment.
“Discontinuing can lead to worsened insulin resistance, and gaining more fat tissue than had been lost,” Chen says. “This may be dangerous, with some patients ending up in a worse situation after stopping than they were before starting.”
This raises difficult clinical and policy questions about how to ensure continuity of care once the demonstration programme concludes, and how to counsel older adults about the long-term commitment that GLP-1 therapy may represent.
The continuing role of medical reconciliation and deprescribing
The findings reinforce the importance of established tools for managing medication burden in older adults, rather than relying on a single new drug class to resolve polypharmacy.
“The tried-and-true methods for polypharmacy are medical reconciliation and rational deprescribing,” says Chen. “Many of these approaches, developed by and publicized by the National Institutes of Health-funded U.S. Deprescribing Research Network, are effective tools for geriatricians and primary care doctors.”
The researchers conclude that medication burden must remain front of mind when treating older adults, and that further research is needed to clarify how obesity medications affect health outcomes specifically in this age group.
Additional authors on the study include Ashwin Chetty, John Batsis, MD, and Kasia Lipska, MD, MHS.
Source: Yale School of Medicine
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Semaglutide Shows Benefit in Severe, Long-Standing Treatment-Resistant Obesity, Trial Finds
Key Takeaways:
- Weekly semaglutide (2.4 mg) cut BMI by an average of 19 per cent – around 22.3 kg – over 68 weeks in young adults with treatment-resistant severe obesity.
- Benefits went beyond weight, with large falls in total, abdominal and liver fat and in metabolic syndrome severity, lowering cardiovascular and type 2 diabetes risk.
- The drug was safe and well tolerated, with only mild, short-lived side effects and no related dropouts.
A promising option for hard-to-treat obesity
A weekly dose of semaglutide (2.4 mg) leads to a clinically significant reduction in body mass index (BMI) and related health outcomes in young adults living with severe obesity who are resistant to treatment following hospital-based, non-pharmacological obesity care during childhood. That is the finding of a randomised controlled trial being presented at this year’s European Congress on Obesity (ECO).
The study, led by researchers from the University of Copenhagen and Holbæk Hospital in Denmark, highlights the importance of identifying as early as possible the children who are resistant to hospital-based obesity care and who may benefit from the timely addition of semaglutide or other glucagon-like peptide-1 receptor agonists (GLP-1 RAs).
Semaglutide and other GLP-1 RAs work by mimicking naturally produced incretin hormones. These hormones help to lower blood sugar levels after a meal and reduce appetite, prompting people to eat less.
Why new strategies are urgently needed
Children living with obesity are five times as likely to be living with obesity in adulthood as their healthy-weight counterparts [1]. Obesity that begins in early childhood carries significant health risks in early adulthood, including early-onset type 2 diabetes, cancer, cardiovascular disease and a reduced quality of life.
Hospital-based, non-pharmacological obesity care – which involves supporting children living with obesity and their families to improve health and thriving during growth and development – has been shown to reduce childhood obesity. However, around one in four children are more difficult to treat, and any reduction in the degree of obesity is hard to maintain. New, effective and safe treatment strategies are therefore urgently needed.
Inside the RESETTLE trial
In the new RESETTLE trial – a randomised, placebo-controlled, double-blind study – the researchers investigated the effect of semaglutide treatment in young adults (aged 18 to 28 years) who were still living with severe obesity despite at least one year of treatment at the Children’s Obesity Clinic, European Centre for Obesity Management, at Holbæk Hospital in Denmark.
The study involved 246 young adults (average age 23 years, 59 per cent female) who had been included in the HOLBAEK Study [2]. Participants were randomised into four different groups, based on how they had previously responded to the paediatric hospital-based treatment programme and on their current BMI:
- 82 participants with a low response to childhood obesity care (a change in BMI that was not enough to improve their health) and who were currently living with obesity as young adults (BMI of 30 kg/m² or above).
- 80 participants with a medium response to childhood obesity care and living with obesity as young adults (BMI of 30 kg/m² or above).
- 34 participants with a high response to childhood obesity care who were not living with obesity as young adults (BMI below 30 kg/m²).
- 50 participants from a population-based reference group who had a normal weight development in childhood.
What the assessments measured
All participants, regardless of their response group, underwent examinations of cardiometabolic biomarkers (waist circumference; lipids in the blood, including cholesterol; blood glucose; and blood pressure), full-body dual-energy x-ray absorptiometry (DXA) imaging of body composition, and magnetic resonance imaging (MRI) of liver and visceral (abdominal) fat.
The 162 participants in the low- and medium-response groups – who had poorer health outcomes than the high-response and normal-BMI-development groups – were randomly assigned to either weekly injections of semaglutide (2.4 mg; 54 in the low-response group and 55 in the medium-response group) or placebo (28 and 25 respectively) over 68 weeks. In total, 152 participants (94 per cent) attended the final visit.
Results: large reductions in BMI and weight
After 68 weeks, semaglutide led to an average decrease in BMI of 19 per cent (average weight loss of 22.3 kg) in both the low- and medium-response groups, compared with placebo.
In the low-response group, average BMI among those taking semaglutide fell by 7.3 kg/m² (from 40.5 kg/m²), compared with a minor increase of 0.5 kg/m² in the placebo group. Similarly, in the medium-response group, average BMI decreased by 6.7 kg/m² (from 38.0 kg/m²) among those taking semaglutide, but rose by 0.6 kg/m² among those given placebo (see figure 1 in the full abstract).
Beyond weight: fat and metabolic health
Participants in the low- and medium-response groups who received semaglutide also saw substantial improvements in total fat mass (-17 kg and -15 kg respectively), abdominal fat (-48 per cent and -41 per cent) and liver fat (-39 per cent and -34 per cent) compared with placebo – all key factors in reducing obesity-related health risks.
In addition, these participants experienced substantial improvements in their metabolic syndrome severity score (-0.80 and -0.58), a measure that integrates lipids, blood pressure, fasting glucose and waist circumference into a single value. This reflects a substantial reduction in the risk of developing cardiovascular disease and type 2 diabetes.
Safety and tolerability
Semaglutide was safe and generally well tolerated. Gastrointestinal side effects, such as nausea and abdominal pain, were the most common. However, most side effects were manageable, resolved over time, and did not lead to participants dropping out of the trial.
What the researchers say
“By reducing the degree of obesity and improving cardiometabolic health irrespective of prior response to childhood obesity care, GLP-1 based treatment could help more young people with severe obesity to reduce their burden of obesity-related complications in early adulthood,” said author Joachim Holt from the University of Copenhagen.
According to study lead Professor Signe Sørensen Torekov at the University of Copenhagen, “Severe obesity in young people is a complex, chronic disease with serious health consequences. GLP-1 based treatment offers a promising option for managing severe obesity in young people who are resistant to prior hospital-based non-pharmacological care. Importantly, supporting families to implement increased physical activity and health behaviours should remain the foundation of all treatments for childhood obesity and prevention of obesity across generations.”
Head consultant Jens-Christian Holm, of the Children’s Obesity Clinic, European Centre for Obesity Management, Holbæk University Hospital, adds that, “Childhood obesity is a chronic disease resulting in numerous complications reducing physical, mental and social thriving during growth and development. Being able to optimise obesity treatment with the addition of drugs in selected patients to improve health is a worldwide imperative.”
CCH insights:
Once again, GLP-1 therapy delivers excellent results, providing the necessary change in appetite that allowed these young people to make the behavioural changes needed to lose weight and improve health, when previously they had been unable to do so. And it is not just about losing weight, with significant improvements in metabolic and cardiovascular disease risk factors.
References:
[1] Predicting adult obesity from childhood obesity: a systematic review and meta‐analysis – Simmonds – 2016 – Obesity Reviews – Wiley Online Library
[2] The HOLBAEK Study includes more than 4,000 Danish children and adolescents with and without obesity (Study Details | NCT02852694 | Reduce Risk for Crohn’s Disease Patients | ClinicalTrials.gov).
Genetics May Help Explain Why GLP-1 Weight-Loss Drugs Work Better for Some People Than Others
Key Takeaways:
- Researchers have identified two genetic variants that may help explain why people respond differently to GLP-1 weight-loss medications such as Wegovy and Mounjaro.
- One genetic variant was linked to slightly greater weight loss, while another appeared to increase the likelihood of nausea and vomiting in people taking tirzepatide.
- Experts say the findings are important for understanding treatment variability, but non-genetic factors such as sex, medication type, dosage and treatment duration still appear to play a much larger role.
Genetic differences may help explain variable responses to GLP-1 weight-loss drugs
Scientists have uncovered new evidence suggesting that genetics may partly explain why GLP-1 weight-loss medications produce very different results from one person to another.
The research, published in Nature, examined how specific genetic differences may influence both weight-loss outcomes and the risk of side-effects in people taking glucagon-like peptide-1 receptor agonists, commonly known as GLP-1 drugs.
The findings could eventually contribute to more personalised approaches to obesity treatment, where therapies are selected based on an individual’s biological profile. However, researchers and independent experts stressed that the genetic effects identified in the study were relatively modest and are not yet strong enough to guide routine clinical decisions.
GLP-1 medicines and their growing role in obesity care
GLP-1 receptor agonists, including semaglutide, sold under the brand name Wegovy, and tirzepatide, marketed as Mounjaro, mimic naturally occurring gut hormones involved in regulating appetite, digestion and insulin release.
These medicines have transformed obesity treatment in recent years and are now used by millions of people globally. By helping reduce appetite and slow gastric emptying, they can support significant weight loss in many individuals.
However, clinical experience and research have consistently shown substantial variation in treatment response. Some people lose large amounts of weight, while others experience more limited benefits. Similarly, side-effects such as nausea and vomiting can vary considerably between individuals.
Until now, the biological reasons behind these differences have remained poorly understood.
Large genetic analysis involving nearly 28,000 people
To investigate the issue, researchers from 23andMe and a nonprofit medical research institute analysed data from 27,885 people taking GLP-1 medications.
The study focused on variations in genes linked to gut hormone pathways that regulate appetite and digestion.
Researchers identified one GLP1 receptor variant, known as rs10305420, that was associated with slightly greater weight loss among people carrying the variant compared with those who did not carry it.
A second genetic variant, rs1800437, was linked to a greater likelihood of nausea and vomiting in people taking tirzepatide. However, this variant was not associated with the amount of weight lost.
The findings suggest that inherited genetic differences may contribute to how people respond to GLP-1 therapies, both in terms of effectiveness and tolerability.
Genetics appears to play only a modest role
Despite the findings, researchers emphasised that the overall contribution of genetics appeared relatively small.
Marie Spreckley, an obesity expert at the University of Cambridge who was not involved in the study, said the research offered biologically plausible evidence that genetic variation may influence treatment outcomes.
“However, the magnitude of these genetic effects is small in clinical terms,” she said. “Importantly, non-genetic factors such as sex, drug type, dose and duration appear to explain a substantially larger proportion of variability. The authors’ model suggests that most of the explained variance comes from these factors, with genetics adding only a modest incremental contribution.
“In terms of how this fits with the wider evidence, it reinforces that while there is substantial variability in response to GLP1 therapies, genetics is only one part of a much more complex picture. Behavioural, clinical and treatment-related factors remain the dominant drivers of outcomes.
“Overall, this is an important step toward understanding variability and the potential for future precision approaches, but the effects are modest and the evidence is not yet sufficient to support using genetic information to guide treatment decisions in routine clinical practice.”
Toward more personalised obesity treatment
The findings contribute to a growing body of research exploring precision medicine approaches in obesity care.
As scientists continue to investigate why individuals respond differently to treatments, future obesity management may increasingly incorporate biological, behavioural and clinical information to tailor therapies more effectively.
However, experts caution that current evidence does not support the use of genetic testing to determine which GLP-1 medication a person should receive.
Instead, the study primarily advances understanding of the complex biological factors that may influence treatment response, while reinforcing that genetics represents only one piece of a much larger puzzle involving lifestyle, clinical characteristics and medication-related factors.
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Weight Loss Drugs Linked to Lower Risk of Peptic Ulcer Disease in Adults with Diabetes
Key Takeaways:
- A large US study involving more than 66,000 adults found that people with type 2 diabetes using GLP-1 receptor agonists had significantly lower odds of developing peptic ulcer disease.
- Researchers observed a 44 percent lower likelihood of peptic ulcer disease among GLP-1 users overall, with a 56 percent lower risk seen in people who switched from metformin to a GLP-1 medication instead of insulin.
- The findings add to growing evidence that GLP-1 receptor agonists may have anti-inflammatory and gastrointestinal protective effects beyond blood sugar control and weight management.
Study suggests potential gut benefits of GLP-1 medications
Medications commonly prescribed for type 2 diabetes and obesity management may provide an additional benefit beyond blood sugar control and weight reduction. A large nationwide study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) has found that people with type 2 diabetes who used GLP-1 receptor agonists were significantly less likely to develop peptic ulcer disease compared with those who did not use these medications.
The findings were published in Clinical Gastroenterology and Hepatology and were based on electronic health record data from more than 66,000 adults participating in the National Institutes of Health’s All of Us Research Program. The programme is considered one of the most diverse biomedical research datasets in the United States.
“Peptic ulcer disease remains a significant cause of illness and hospitalization, particularly among people with type 2 diabetes, yet large-scale clinical studies examining how newer diabetes medications affect ulcer risk have been lacking,” said Trisha Pasricha, MD, MPH, a gastroenterologist at BIDMC. “Our study was designed to address that gap and to better understand whether GLP1 receptor agonists are associated with meaningful differences in ulcer risk in this population.”
Understanding peptic ulcer disease in diabetes
Peptic ulcers are painful open sores that develop in the lining of the stomach or upper part of the small intestine. Symptoms can include ongoing abdominal pain, nausea, indigestion, and bloating. In more severe cases, ulcers can lead to complications such as gastrointestinal bleeding or perforation.
Globally, around four million people experience ulcer-related complications each year.
People living with type 2 diabetes are known to have a higher risk of developing peptic ulcer disease. Researchers believe this increased vulnerability may stem from a combination of chronic inflammation, metabolic stress, impaired tissue repair, and greater exposure to medications associated with ulcer formation, particularly nonsteroidal anti-inflammatory drugs (NSAIDs).
Because of this elevated risk, researchers sought to investigate whether GLP-1 receptor agonists, which were first approved for diabetes treatment approximately two decades ago and are now widely used for both diabetes and obesity care, might influence ulcer risk.
GLP-1 use associated with lower ulcer risk
The researchers found that the use of GLP-1 medications was associated with substantially lower odds of being diagnosed with peptic ulcer disease.
Across the full study population, people with type 2 diabetes using GLP-1 receptor agonists had a 44 percent lower likelihood of receiving a peptic ulcer diagnosis compared with people not using these medications. The association remained even after adjusting for factors including age, sex, body mass index, medication use, and other clinical variables.
The investigators also carried out a more focused comparison involving people who had discontinued metformin, which remains the standard first-line therapy for type 2 diabetes. Researchers examined participants who then transitioned either to a GLP-1 medication or to insulin therapy.
In this head-to-head analysis, people who switched to a GLP-1 receptor agonist had a 56 percent lower risk of developing peptic ulcer disease compared with those who switched to insulin.
Researchers point to possible anti-inflammatory effects
Although GLP-1 receptor agonists are not currently prescribed for ulcer prevention, researchers believe the findings may reflect broader biological effects of the medications.
“Although these medications are not prescribed with ulcer prevention in mind, there is growing evidence that GLP1 receptor agonists may have broader biological effects, including anti-inflammatory properties and roles in gastrointestinal mucosal protection,” said senior author Pasricha, who is also an assistant professor of medicine at Harvard Medical School. “Those effects may help explain why we observed different ulcer risks compared with insulin.”
GLP-1 receptor agonists are best known for improving blood glucose control, supporting weight loss, and reducing cardiovascular risk in people with type 2 diabetes and obesity. However, a growing body of research suggests these drugs may also reduce inflammation and support tissue repair within the gastrointestinal tract.
The authors noted that more research is needed to determine whether these effects directly improve the stomach and small intestine’s ability to resist injury, particularly in people with diabetes who may already have impaired protective mechanisms.
Findings strengthened by known risk factors
The investigators also observed that medications already known to increase ulcer risk behaved as expected within the dataset. NSAIDs, corticosteroids, and blood thinners were all associated with increased ulcer risk, supporting the reliability of the study’s methodology.
Taken together, the researchers said the findings strengthen the observed association between GLP-1 receptor agonist use and lower rates of peptic ulcer disease.
Study authors and funding
Co-authors of the study included Philippa Seika, Jocelyn Chang, Su Min Hong, Sarah Ballou, Vikram Rangan, Chethan Ramprasad, Johanna Iturrino, Judy Nee, and Subhash Kulkarni of BIDMC; Christian Denecke of Charité Universitätsmedizin; and Anthony Lembo of Cleveland Clinic.
The study was funded by the American Gastroenterological Research Foundation’s Research Scholar Award, the National Institute on Aging, the Diacomp Foundation, a Pilot Grant from the Harvard Digestive Disease Core, and the Walter Benjamin Fellowship from the Deutsche Forschungsgemeinschaft.
The authors reported no conflicts of interest.
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Bariatric Surgery Delivers Greater Weight Loss and Disease Remission Than GLP-1 Drugs, Large Analysis Finds
Key Takeaways:
- A large real-world analysis involving more than 430,000 patients found that metabolic and bariatric surgery produced substantially greater weight loss than GLP-1 medications after 12 months.
- Surgery was associated with higher remission rates for obesity-related conditions including type 2 diabetes, hypertension and high cholesterol.
- Researchers and clinicians said GLP-1 medications represent an important advance in obesity care, but cautioned that they should not be viewed as a replacement for metabolic and bariatric surgery in people requiring more substantial and durable outcomes.
Surgery outperformed GLP-1 drugs across key outcomes
Metabolic and bariatric surgery may provide significantly greater weight loss and higher rates of obesity-related disease remission than glucagon-like peptide-1 receptor agonist medications, according to a major new real-world comparison presented at the American Society for Metabolic and Bariatric Surgery (ASMBS) Annual Meeting 2026.
The systematic review and analysis, described as one of the largest and most comprehensive comparisons of the two treatment approaches to date, evaluated data from 30 clinical studies involving more than 430,000 patients. Researchers found that although both treatments produced meaningful clinical benefits for people living with obesity, metabolic and bariatric surgery consistently outperformed GLP-1 therapies across all major outcomes assessed.
The research was conducted by investigators from Yale School of Medicine, Coreva-Scientific, Vanderbilt University and UT Health San Antonio.
Greater weight loss after surgery
According to the findings, people who underwent metabolic and bariatric surgery experienced more than 20% greater weight loss at 12 months compared with those treated with GLP-1 receptor agonist medications.
Researchers also reported that surgery was linked to substantially higher remission rates for several obesity-related health conditions. Compared with GLP-1 therapy, metabolic and bariatric surgery was associated with:
- 42% higher remission rates for type 2 diabetes
- 12.8% higher remission rates for hypertension
- 20.8% higher remission rates for high cholesterol
The analysis focused specifically on studies that directly compared bariatric surgery with GLP-1 receptor agonists. Studies that combined surgery and medication therapies were excluded from the review.
The primary endpoint examined was weight loss at 12 months. Secondary endpoints included remission of obesity-related conditions such as type 2 diabetes, hypertension and hyperlipidaemia.
Researchers highlight durability of surgical outcomes
The study authors noted that although GLP-1 medications have transformed obesity treatment and expanded evidence-based care options, metabolic and bariatric surgery continues to deliver greater and more durable results for many patients.
“While GLP-1 medications are an important advance, they do not match the magnitude or durability of outcomes achieved with metabolic and bariatric surgery, which remains one of the most underutilized treatments in medicine. Once the medications are discontinued, whether due to side effects, cost or other factors, their benefits often diminish or disappear, whereas the benefits of surgery endure.” – John M. Morton, MD, MPH, FASMBS, Study Co-Author, Professor of Surgery and Vice-Chair, Quality, Surgery at Yale School of Medicine
The findings add to ongoing discussions within obesity care about how best to position GLP-1 therapies and surgical interventions within long-term treatment pathways.
Evidence gap in direct comparisons
Despite the rapid growth in the use of GLP-1 medications such as semaglutide and tirzepatide, researchers noted that direct comparisons between these drugs and bariatric surgery remain limited.
The review involved a comprehensive search of PubMed and EMBASE databases to identify relevant studies comparing the two treatment approaches.
Commenting on the findings, an independent obesity surgery expert said the analysis helps address a major evidence gap in the field.
“Despite the explosive growth of GLP-1 drugs, no randomized controlled trials have directly compared them to bariatric surgery. This analysis helps fill that evidence gap,” said John Scott, MD, FACS, FASMBS, clinical professor of surgery at the University of South Carolina School of Medicine Greenville and metabolic and bariatric surgery director for Prisma Health, who was not involved in the study.
“GLP-1s have expanded evidence-based treatment options, but they should not be seen as a replacement for surgery – especially for patients who require the level of outcomes that only metabolic and bariatric surgery can provide.”
Expanding treatment options in obesity care
The findings come amid growing global interest in obesity treatment strategies as the use of GLP-1 receptor agonists continues to rise rapidly. Medications in this class have demonstrated significant effectiveness for weight reduction and metabolic health improvement, but concerns remain regarding long-term adherence, cost, side effects and weight regain after discontinuation.
Metabolic and bariatric surgery, meanwhile, has long been associated with substantial and sustained weight loss as well as improvements in obesity-related conditions such as type 2 diabetes and cardiovascular risk factors. However, experts have repeatedly argued that surgery remains significantly underutilised despite its established effectiveness.
The researchers concluded that while both treatment approaches play an important role in obesity management, metabolic and bariatric surgery continues to provide the most substantial improvements in weight loss and disease remission outcomes based on current comparative evidence.
Source: American Society for Metabolic and Bariatric Surgery
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People Judge Weight Loss More Harshly When GLP-1 Drugs Are Used, Study Finds
Key Takeaways:
- People using GLP-1 and other anti-obesity medications were consistently judged more negatively than those losing weight through diet and exercise alone.
- Researchers found that anti-obesity medication users were perceived as putting in less effort and were therefore viewed as less moral, competent, warm, and deserving of their success.
- The findings suggest that stigma surrounding obesity treatment may discourage people from seeking effective medical care and reinforce harmful misconceptions about obesity and weight loss.
Study explores social attitudes toward weight loss medication
A recent study published in Scientific Reports has found that people who lose weight using anti-obesity medications (AOMs), including glucagon-like peptide-1 (GLP-1) receptor agonists, are often judged more harshly than those who lose weight through diet and exercise alone.
The research examined how the use of anti-obesity medication influences perceptions of effort, morality, competence, warmth, and deservingness. The findings suggest that social attitudes toward obesity treatment remain strongly shaped by beliefs about personal effort and self-control.
With more than one billion people worldwide living with obesity, the researchers noted that how a person loses weight can significantly influence how others perceive them. Although GLP-1 receptor agonists and other anti-obesity medications have demonstrated substantial effectiveness in treating obesity, they are frequently criticised as an “easy way out.”
According to the researchers, this perception reflects a broader psychological phenomenon known as effort moralization – the tendency to associate greater effort with greater moral worth.
The authors explained that such beliefs may reinforce obesity stigma, discourage people from seeking treatment, and negatively affect both physical and mental health outcomes.
While anti-obesity medications can provide important medical support for people living with persistent obesity, the researchers stressed that understanding the social impact of these perceptions is necessary if the full potential of these treatments is to be realised.
Four studies conducted across three countries
The research involved four pre-registered experimental studies conducted between November 2024 and February 2025 in Belgium, the United States, and the United Kingdom.
In total, 1,205 participants took part in the research. Participants were recruited online through university participant pools and the Prolific platform. Researchers applied several quality-control measures, excluding incomplete responses, failed attention checks, overly rapid responses, and participants with insufficient language proficiency.
Across the studies, participants were presented with descriptions of two individuals who shared identical weight-loss goals and similar experiences with diet and exercise. The only difference between the individuals was that one used an anti-obesity medication while the other did not.
Participants then rated both individuals using Likert-type scales assessing:
- Perceived effort
- Moral character
- Warmth
- Competence
- Deservingness of weight-loss success
- Willingness to cooperate with them in future scenarios
The researchers also explored several additional variables across the studies, including:
- General attitudes toward anti-obesity medication
- Personal or social experience with weight-loss medication
- Beliefs that anti-obesity medication represents a “shortcut”
- Personality traits measured using the Big Five Inventory (BFI)
To analyse the data, the researchers used t-tests, correlations, multilevel modelling, and evidence synthesis techniques.
Anti-obesity medication users viewed more negatively
Across all four studies, the findings revealed a consistent pattern of negative social judgement toward individuals using anti-obesity medication.
Compared with people relying solely on diet and exercise, anti-obesity medication users were perceived as putting in less effort into achieving their weight-loss goals.
This perception of lower effort was strongly linked to harsher moral evaluations. Participants consistently rated anti-obesity medication users as less moral than non-users.
In Study 1, for example, significantly lower perceived effort ratings for anti-obesity medication users were accompanied by similarly large reductions in moral character ratings.
The bias extended beyond morality alone.
Participants also viewed anti-obesity medication users as:
- Less competent
- Less warm
- Less deserving of their success
In addition, participants reported lower anticipated satisfaction with future cooperation involving anti-obesity medication users in a hypothetical training-partner scenario.
According to the paper’s evidence synthesis, most of these effects were large, although the effect relating to warmth was more moderate.
Perceived effort was closely tied to moral judgement
One of the most significant findings was the strong relationship between perceived effort and moral judgement.
Across all four studies, larger differences in perceived effort between medication users and non-users were associated with larger differences in moral evaluations.
The researchers concluded that perceptions of effort appear to play a major role in shaping broader social judgement.
The findings support the idea that many people continue to associate moral worth with visible personal struggle and self-discipline, particularly in relation to body weight and weight loss.
“Shortcut” beliefs intensified negative bias
The study also examined factors that influenced the strength of these perceptions.
Participants who held more positive views toward anti-obesity medications, or who had prior personal or social experience with such treatments, tended to judge medication users less harshly.
In contrast, stronger beliefs that anti-obesity medication represents a “shortcut” to weight loss were associated with more negative moral judgements.
In some analyses, these shortcut beliefs also amplified the relationship between perceived effort and bias.
The researchers found that personality traits such as conscientiousness and extraversion had little overall effect on participants’ judgements. This suggests that the bias is driven more by beliefs about effort and treatment legitimacy than by broader personality characteristics.
One exploratory analysis identified a small association with neuroticism, although this effect was limited.
Meta-analytic evidence synthesis across the studies confirmed that most effects were large, particularly for:
- Perceived effort
- Moral judgement
- Competence
- Cooperation satisfaction
- Deservingness
Effects relating to warmth were moderate by comparison.
Findings highlight social challenges surrounding obesity treatment
The researchers concluded that using anti-obesity medication is not simply a medical decision, but also a social one that may expose individuals to stigma and negative judgement.
According to the findings, people using anti-obesity medications are frequently perceived as putting in less effort and are therefore judged as less moral, less competent, and less deserving of success.
Although the studies were based on vignette scenarios rather than real-world interactions, the researchers stated that the findings point toward a widespread bias rooted in effort moralization.
They suggested that these attitudes could influence interpersonal relationships, healthcare experiences, and broader public perceptions of obesity treatment.
The authors argued that addressing these misconceptions is important for improving healthcare quality and reducing obesity-related stigma.
They also suggested that public education and changes in the way weight loss is discussed may help shift attention away from perceived effort and toward health outcomes and overall well-being.
CCH insights:
Unfortunately, this shows that there is still a very poor understanding of obesity amongst the general public, which means that biased, negative attitudes towards people with excess weight persist. Instead of being seen as medical tools to treat a complex chronic condition, GLP-1 medications are seen by many as short-cut for weight loss cheats. Current evidence suggests these attitudes are common even within the health professions. To improve the quality of obesity care, and to encourage those who need help to seek it, these misconceptions must be addressed.
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GLP-1 Weight Loss Is Mostly Driven by Fat Loss, Not Muscle
Key Takeaways:
- GLP-1 receptor agonists and dual GLP-1/GIP therapies lead to significant weight loss, primarily through reductions in fat mass rather than muscle.
- Improvements in body composition, including reductions in visceral fat, occur as early as three months into treatment.
- Although some lean body mass loss is observed, it is relatively modest compared with overall weight loss, suggesting a favourable pattern of change.
GLP-1 therapies in the context of obesity care
A recent study published in the International Journal of Obesity examined how glucagon-like peptide 1 receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide agonists affect body weight and composition in adults living with overweight or obesity.
The global prevalence of obesity has risen substantially in recent decades. This condition is closely linked to a range of cardiometabolic complications that can reduce both quality of life and life expectancy. As a result, effective obesity management typically requires a personalised, multidisciplinary approach. This may include behavioural support, dietary changes, physical activity, pharmacological treatments, and, in some cases, surgical intervention.
GLP-1 receptor agonists and related incretin-based therapies have emerged as an important pharmacological option. These treatments are known to support sustained weight loss and improve obesity-related comorbidities. They have also demonstrated cardioprotective effects. However, while these therapies predominantly reduce fat body mass, they may also lead to some loss of lean body mass, which has raised concerns, particularly for older adults and people at risk of frailty.
Study design and methods
To better understand these effects, researchers conducted a comprehensive evaluation of clinical studies assessing GLP-1-based therapies and their impact on body composition.
Databases including Web of Science, PubMed, and Scopus were systematically searched for relevant studies involving adults with overweight or obesity, with or without type 2 diabetes. Following removal of duplicate records, studies were screened based on titles, abstracts, and full texts to determine eligibility.
The methodological quality of the included studies was assessed using established tools. Meta-analyses were then performed on studies that provided numerical data on changes in body composition and anthropometric measures. Statistical analyses used random-effects models, with subgroup analyses based on drug type and treatment duration. Publication bias was evaluated using Egger’s test.
In total, 36 studies were included in the qualitative review, with 24 contributing to the meta-analyses. Most studies were conducted in Europe and Asia, and many reported outcomes at six months. Twenty-four studies included people living with type 2 diabetes. The most frequently studied medications were liraglutide and semaglutide. Body composition was commonly assessed using bioelectrical impedance analysis and dual-energy X-ray absorptiometry.
Changes in weight and body composition
Early effects at three months
After three months of treatment, participants experienced a significant reduction in body mass of approximately 9 percent. This effect was particularly notable among those receiving beinaglutide.
Substantial improvements in body composition were also observed. Visceral adipose tissue area decreased by 29.25 cm², while fat body mass was reduced by 17 percent. Lean body mass showed a smaller but statistically significant reduction of 2 percent.
In addition, body mass index decreased by 2.96 kg/m² and waist circumference by 9.6 cm.
Outcomes at six months
At six months, body mass remained significantly reduced, with an average decrease of 5 percent.
Both fat body mass and lean body mass declined further, by 6 percent and 1 percent respectively. Skeletal muscle mass showed a modest reduction of 3 percent. Visceral adipose tissue continued to decrease, with a reduction of 32.31 cm².
Body mass index fell by 2.40 kg/m², while waist circumference decreased by 2.3 cm.
Longer-term results at twelve months
At twelve months, body mass was reduced by 4 percent, with continued decreases in body mass index of 1.74 kg/m² and waist circumference of 3.2 cm.
Both fat body mass and lean body mass were reduced by 4 percent. The most pronounced reductions were reported in a study involving liraglutide, although the authors noted considerable variability between studies and advised caution when comparing specific agents.
Egger’s test indicated some publication bias in outcomes reported at three months, but no significant bias was observed at later time points.
Interpreting fat loss and muscle preservation
Overall, the findings demonstrate that GLP-1-based therapies produce meaningful improvements in key measures associated with obesity, including body mass, body mass index, and waist circumference, across multiple time points.
The most rapid and substantial changes occurred within the first three months of treatment. Across all timeframes, reductions in fat mass, particularly visceral fat, were more pronounced than reductions in lean mass.
The authors described this pattern as “quality” weight loss, characterised by a predominance of fat mass reduction with relative preservation of lean tissue. Importantly, no single GLP-1 receptor agonist was found to be superior in preserving lean mass.
Implications for clinical practice and future research
These findings have important implications for clinical care. While some degree of lean mass loss occurs with GLP-1-based therapies, the overall pattern of weight loss appears favourable, particularly given the substantial reductions in fat mass and visceral adiposity.
Future research should focus on optimising treatment strategies that combine pharmacotherapy with lifestyle interventions. In particular, there is a need to explore approaches that support the preservation of lean mass, such as targeted nutritional strategies and resistance training programmes.
Such considerations are especially important for people at higher risk of sarcopenia, including older adults and those with existing muscle loss.
CCH insights:
These results are encouraging, but it is important not to become complacent about lean mass loss during weight loss. The studies analysed here involved average weight losses of less than 10% of body weight, but some people can lose 15-20% of body weight on GLP-1 therapy – do they lose similar proportions of body fat and lean tissue? All patients on GLP-1 therapy should receive advice on lifestyle measures to help minimise lean tissue loss.
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New Study Suggests Semaglutide May Reduce Epilepsy Risk in Adults with Type 2 Diabetes
Key Takeaways:
- Initiating semaglutide was associated with a significantly lower risk of developing epilepsy or seizures compared with other glucose-lowering therapies.
- The observed effect does not appear to be primarily driven by improvements in blood glucose or body weight.
- Findings are preliminary and should be interpreted as an early signal rather than a basis for changing clinical practice.
Background – seizure risk in type 2 diabetes
People living with type 2 diabetes mellitus face a higher risk of developing seizures and epilepsy. This increased risk is thought to be partly driven by inflammatory processes that affect the central nervous system. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are primarily used for glucose regulation, there has been growing scientific interest in their potential neurological effects.
However, until now, the relationship between GLP-1 RAs and seizure risk has remained unclear.
Study design and population
The findings were presented at the American Academy of Neurology Annual Meeting, held in Chicago from April 18 to 22, 2026.
Researchers conducted a retrospective study using a target trial emulation approach, drawing on data from the National Institutes of Health All of Us Controlled Tier Dataset. The analysis focused on adults aged 18 years and older with type 2 diabetes mellitus who initiated one of the following treatments between December 2018 and December 2021:
- Semaglutide
- Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors)
- Other glucose-lowering therapies
Participants were followed through to December 2023.
To ensure comparability between groups, inverse probability of treatment weighting was applied to balance baseline characteristics. Time-to-event analyses were then used to assess the risk of developing epilepsy or seizures.
Cohort characteristics
A total of 393,596 individuals met eligibility criteria. Within this population:
- 8,533 individuals were included in the semaglutide versus other glucose-lowering drug comparison (2,397 vs 6,136)
- 7,455 individuals were included in the semaglutide versus SGLT2 inhibitor comparison (1,650 vs 3,725)
Key findings – reduced risk of seizures
After statistical adjustment, initiation of semaglutide was associated with a lower risk of epilepsy or seizures compared with both comparator groups:
- Compared with other glucose-lowering drugs:
- Hazard ratio: 0.46
- 95% confidence interval: 0.25–0.83
- P = .010
- Compared with SGLT2 inhibitors:
- Hazard ratio: 0.44
- 95% confidence interval: 0.22–0.86
- P = .017
These findings suggest a meaningful reduction in relative risk among those initiating semaglutide.
Absolute risk reduction and clinical interpretation
Further modelling provided estimates of absolute risk reduction:
- Compared with other glucose-lowering therapies:
- Absolute risk reduction: -0.014
- Number needed to treat: 69
- P < .001
- Compared with SGLT2 inhibitors:
- Absolute risk reduction: -0.008
- Number needed to treat: 129
- P < .001
These results indicate that, while the relative risk reduction is notable, the absolute reduction in risk remains modest.
Mechanisms – not driven by glycaemic control alone
To explore potential mechanisms, the researchers conducted mediation analyses. These analyses assessed how much of the observed effect could be explained by changes in glycated haemoglobin or body mass index.
The results showed that:
- Glycated haemoglobin accounted for only 1.1% of the effect compared with other glucose-lowering drugs and 3.6% compared with SGLT2 inhibitors
- Body mass index contributed 0.3% or less in both comparisons
This suggests that the reduced seizure risk may not be primarily driven by improvements in glycaemic control or weight loss, pointing towards other possible mechanisms.
Expert perspective
Yoonhyuk Jang, MD, PhD, Postdoctoral Fellow in the Department of Immunology at Harvard Medical School, commented on the findings:
“This study suggests that semaglutide may be associated with a lower risk of adult-onset seizures or epilepsy in patients with type 2 diabetes, with the signal appearing more pronounced in late-onset cases among adults aged 60 years or older.”
He added:
“Given that age-associated brain insults are major contributors to adult-onset seizures and epilepsy, these findings may have implications beyond seizure risk alone and raise the possibility that semaglutide could also be relevant to broader brain health; however, because this was a retrospective target trial emulation with a relatively small number of events, it is not yet practice-changing and should instead be viewed as a signal that supports further research into the role of GLP-1 receptor agonists in epileptogenesis.”
Limitations and future directions
The authors emphasised that the study design was observational, despite using advanced statistical methods to emulate a clinical trial. As such, causality cannot be definitively established.
Additionally, the relatively small number of seizure events limits the strength of the conclusions. These findings should therefore be interpreted cautiously and seen as hypothesis-generating.
Further prospective and randomised studies will be needed to determine whether GLP-1 receptor agonists such as semaglutide have a direct role in reducing seizure risk or influencing broader neurological health.
Disclosures
One study author reported affiliations with biotechnology, pharmaceutical, or device companies. Full disclosure details are available in the original study source.
Source: Neurology Advisor
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