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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Statins Bring Many People With Obesity Level With Healthy-Weight Peers on Cholesterol and Blood Pressure, Study Finds
Key Takeaways:
- Among adults over 40 in high-income countries, gaps in cholesterol and blood pressure between people with obesity and those of a healthy weight have narrowed or vanished.
- The convergence is driven largely by wider use of statins and blood-pressure medications among people living with obesity.
- In adults under 40, people with obesity still show higher cholesterol and blood pressure, and obesity continues to raise the risk of other conditions.
A narrowing gap in cardiovascular risk
Many adults living with obesity now have cholesterol and blood pressure readings that are “indistinguishable” from those of people at a healthy weight, largely because of the use of statins, a major new study has found. In some cases, researchers reported, people with obesity were “better off” than their healthy-weight counterparts.
Historically, adults with obesity were more likely to have raised blood pressure and higher levels of unhealthy cholesterol. The study found, however, that differences in unhealthy cholesterol and blood pressure have “narrowed or disappeared” among people aged 40 and over.
Experts attribute the shift chiefly to the greater use of cholesterol-lowering medications, such as statins, and blood-pressure treatments – both of which are more commonly prescribed to people living with obesity. They said the findings were important to “give a picture of the cardiovascular health” of the population most likely to be offered weight-loss medications, whose popularity has risen rapidly, and warned that it was important not to “lose sight” of these results as more people take such drugs.
What the researchers examined
The study, published in the Lancet, drew on data from almost 1 million adults aged 20 to 79 across England, Japan, South Korea, Taiwan, Thailand, Finland and the United States. Researchers analysed blood pressure, cholesterol levels and body mass index (BMI) scores recorded in 110 health surveys carried out between 1990 and 2024. They also reviewed the use of cholesterol-lowering drugs and blood-pressure treatments, known as antihypertensives.
The team found that unhealthy cholesterol levels and blood pressure “declined over time”, particularly among people aged 40 and over. Those declines were larger among people with obesity, “leading to a convergence of these risk factors between obesity and normal BMI in people older than 40 years”.
The researchers wrote: “As a result of these trends, in England, the US, Thailand, South Korea, and Japan, older people with obesity often became indistinguishable from, or better off than, those with normal BMI in terms of non-HDL cholesterol and SBP (systolic blood pressure).”
They added: “We found that differences in non-HDL cholesterol and SBP between those with obesity and those with a normal BMI narrowed or disappeared, especially in older adults, in some cases making those with and without obesity indistinguishable in terms of these cardiometabolic traits.”
Why the gap has closed
Prof Majid Ezzati, from the School of Public Health at Imperial College London, said: “Our study suggests that, in high-income countries, taking medication to lower blood pressure and cholesterol has helped middle-age and older adults lower their cardiovascular risk to levels that are similar to people with normal BMI [body mass index].
“At a time that weight-loss medications are becoming more widely used, our results give a picture of the cardiovascular health of people likely to be prescribed them, which allows the healthcare system to understand how blood pressure and cholesterol treatments benefit the population alongside weight-loss medications.”
Younger adults remain at higher risk
The convergence was not seen across all age groups. In adults under 40, people with obesity still had higher levels of unhealthy cholesterol and higher blood pressure than their healthy-weight peers.
One of the research team, Prof Edward Gregg from Imperial College London, stressed that “it doesn’t mean that obesity does not still increase your risk of other outcomes”.
Another of the authors, Yse d’Ailhaud de Brisis, also from Imperial College London, said: “While good news for older adults with obesity, our results suggest that cardiovascular health risks remain higher for adults under 40 than for their counterparts with a normal BMI.
“Early lifestyle interventions, screening and, when appropriate, medication in this younger group should be considered to prevent long-term cardiovascular complications linked to obesity.”
A public health success, with caveats
Commenting on the study, Prof Bryan Williams, the chief scientific and medical officer at the British Heart Foundation, said: “This study highlights a powerful public health success story – it shows just how effective modern treatments for blood pressure and cholesterol have become, with many people over 40 with obesity now reaching levels similar to those with a healthy weight.
“But we must not lose sight of the bigger picture. These medications are needed because of the adverse effects of obesity on cardiovascular disease risk. Moreover, obesity still affects the body in many other ways and increases the risk of other health problems, including diabetes, kidney disease and some cancers.”
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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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Tirzepatide May Activate Calorie-Burning Brown Fat in Obesity, Trial Suggests
Key Takeaways:
- Findings from the TABFAT trial, presented at ENDO 2026, indicate that tirzepatide does more than curb appetite – it also appears to activate brown adipose tissue, a heat-producing fat that burns calories.
- Among premenopausal women with obesity, the proportion with PET/CT-detectable brown fat activity rose from 41.2% to 64.7% after 24 weeks of treatment, with no comparable change in the placebo group.
- Researchers also saw potential signs of white fat taking on more metabolically active “beige” characteristics, pointing towards future therapies that pair appetite control with increased energy expenditure.
Beyond appetite: a different question
For people taking tirzepatide, weight loss has so far been explained mainly by a reduced appetite and the smaller portions that follow. New research suggests the picture may be more complex. The medication appears to do more than dampen hunger – it also seems to switch on brown adipose tissue, a metabolically active fat that generates heat and consumes calories. The findings, described by the research team as a notable milestone in obesity research, were due to be presented on Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
The study set out to look past the appetite-suppressing effect that has dominated explanations of how these medications work. As lead investigator Rok Herman, M.D., of the Department of Endocrinology, Diabetes and Metabolic Diseases at University Medical Centre Ljubljana in Ljubljana, Slovenia, put it: “In the TABFAT trial, we asked a different question: beyond eating less, does tirzepatide also change how the body burns energy – specifically through brown adipose tissue, a metabolically active type of fat that produces heat and consumes calories?”
What is brown adipose tissue?
Brown adipose tissue, often referred to as brown fat, was for many years thought to disappear after infancy. Its presence in adults was only confirmed through imaging studies in the late 2000s. Unlike ordinary white fat, which mainly stores energy, brown fat burns it to produce heat. In people living with obesity this tissue is markedly suppressed, and until now moderate cold exposure has been its strongest recognised activator.
How the TABFAT trial was designed
The team led by Herman ran a randomised, placebo-controlled clinical trial in premenopausal women with obesity. To assess what was happening within the tissue itself, the researchers used cold-stimulated PET/CT imaging alongside MRI scans, measuring brown adipose tissue activity both before treatment and after 24 weeks. Using more than one imaging method allowed the team to capture different aspects of brown fat biology rather than relying on a single measure.
What the scans revealed
The results pointed to a measurable change in how the body handled energy, not simply how much participants ate. “We found that tirzepatide significantly increased brown adipose tissue activity and volume, and it also showed potential signs of converting white subcutaneous fat into more metabolically active ‘beige’ fat,” Herman said.
The shift was clear in the imaging data. Tirzepatide increased PET/CT-detectable brown adipose tissue activity from 41.2% to 64.7% of participants, while no comparable change was seen in the placebo group. The researchers were reassured that the effect showed up across the different scanning techniques used. “We were also encouraged by the consistency of the signal across other imaging modalities employed in the study that may capture different component of brown fat biology,” Herman added.
Why this matters for obesity care
The findings suggest a fuller account of how the latest anti-obesity medications work. Rather than acting on appetite alone, tirzepatide also appears to influence how much energy the body burns at the level of the tissue. “This adds a new layer to how we understand the new generation of anti-obesity medications,” Herman said. “They are not only appetite suppressants – tirzepatide also appears to modulate energy expenditure at the tissue level, opening a plausible path toward future therapies that combine appetite regulation with thermogenic activation.”
Looking ahead
Herman suggests that future research should measure, study and potentially enhance brown and beige fat activity, treating it as a specific target within a more tailored approach to obesity care. If brown fat activation can be reliably encouraged and built upon, it may complement the appetite-related effects already well documented, broadening the options available to people living with obesity.
This article summarises findings presented at ENDO 2026, the Endocrine Society’s annual meeting. Research presented at conferences may not yet have completed full peer review.
Source: Endocrine Society
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GLP-1 Medications Show No Harm to Fertility – and May Benefit Men With Obesity, New Analysis Finds
Key Takeaways:
- A new review of randomised controlled trials found that GLP-1 medications do not harm male hormones, sexual function or sperm quality after long-term use, and in some cases appear to improve them.
- In men with obesity and weight-related low testosterone, treating the underlying excess weight and poor metabolic health may naturally restore hormone levels while preserving fertility – potentially offering an alternative to testosterone replacement therapy.
- The findings are encouraging but preliminary; with only five eligible trials and varying results, the research team stresses that larger, better-designed studies are still required.
A reassuring picture for male reproductive health
Long-term use of GLP-1 medications does not harm male hormones or fertility, according to research being presented on Monday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois. The findings go further still: the research team reported that GLP-1 medications may actually raise testosterone levels and improve sperm quality in men who have obesity-related low testosterone, while simultaneously tackling the metabolic problems that sit beneath those hormonal changes.
How the study was carried out
The work was led by scientists at University Hospitals Coventry and Warwickshire and Warwick Medical School in Coventry, United Kingdom. The team searched medical databases for published randomised controlled trials, narrowing their focus to studies that compared GLP-1 medications against other treatments or a placebo in men aged 18 to 65.
Their primary interest lay in changes to testosterone and the other hormones that govern testicular function. Alongside this, they also assessed sperm quality, body weight, blood sugar, cholesterol and broader markers of metabolic health. To reduce the risk of bias, two independent reviewers checked each study, and five clinical trials ultimately met the eligibility criteria.
What the trials revealed
Across these reports, GLP-1 medications showed no negative effect on hormones, sexual function or sperm quality.
In one 24-week semaglutide study, men saw improvements in sperm shape and cholesterol levels, while their testosterone and other hormone levels remained stable. A separate 16-week liraglutide study, conducted in men with obesity and low testosterone driven by excess weight, found that participants experienced increases in testosterone and related hormones. Notably, their overall health outcomes were better than those achieved with testosterone replacement alone.
Treating the cause rather than the symptom
For the research team, the most significant implication concerns how clinicians approach low testosterone in men with obesity.
“This work supports a shift away from prescribing testosterone replacement in men with obesity and low testosterone and toward treating the underlying cause – excess weight and poor metabolic health – which can naturally restore hormone levels and preserve fertility,” said endocrinologist and team lead Pratibha Natesh, M.B.B.S., M.R.C.P., M.Res., at Warwick Medical School.
Important caveats
While the outcomes are positive, Dr Natesh was careful to temper expectations. The body of evidence remains small and the results vary between studies, so larger and better-designed trials are needed before the effects on male fertility can be fully understood.
She also cautioned that most of the reproductive benefits observed are likely to be indirect, flowing from improved metabolic health rather than from any direct action on the reproductive system. Importantly, GLP-1 medications have not been evaluated as treatments for male infertility or hypogonadism, and should not be regarded as such.
The wider takeaway
By providing clear, evidence-based information about GLP-1 weight-loss and diabetes medications, Dr Natesh hopes the research will help people make better-informed decisions about these treatments.
“Improving metabolic health can have positive effects far beyond weight alone,” she said.
Source: Endocrine Society
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People with Obesity Tend to Move Less After Starting GLP-1 Medications, Study Finds
Key Takeaways:
- Daily step counts and moderate-to-vigorous activity both dropped after adults with obesity started a GLP-1 receptor agonist, with no sign that weight loss prompted people to move more.
- Because these medications strip away lean muscle as well as fat, staying active matters for protecting strength and long-term health rather than being an optional extra.
- This is the first large study to draw on data from wearable fitness trackers in adults taking GLP-1 medications, and its authors argue for targeted support that builds activity in alongside treatment.
A counterintuitive picture of how people move
It is tempting to assume that as the weight comes off, people naturally become more active. New findings suggest the opposite may be closer to the truth. Adults with obesity who were losing weight on glucagon-like peptide-1 (GLP-1) receptor agonist medications significantly reduced their physical activity, according to a study being presented on Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Illinois.
That matters because activity is one of the main safeguards against an unwanted side effect of these treatments. GLP-1 receptor agonists such as semaglutide, liraglutide, dulaglutide and tirzepatide reduce not only fat but also lean muscle mass. This makes physical activity essential for preserving strength and long-term health, according to study lead Sajana Maharjan, M.D., of HSHS St. John’s Hospital in Springfield, Illinois.
How the study was carried out
The work was a retrospective pre–post cohort study, meaning researchers compared the same individuals before and after they started treatment. It drew on data from the National Institutes of Health’s All of Us Research Program, which links participants’ electronic health records with their Fitbit activity data, allowing the team to track real-world movement rather than relying on self-reported habits.
Among the 1,950 adults with obesity who started a GLP-1 medication, researchers studied 753 people who had enough wearable-device data for analysis. The cohort was predominantly female, at 78.6 per cent, with a mean age of 52.7 years.
For each person, the researchers compared physical activity before and after treatment began, focusing on two measures: daily step counts and minutes of moderate-to-vigorous physical activity (MVPA).
Steps and active minutes both fell
The direction of travel was clear. On average, daily steps decreased from 5,047 to 4,487 per day, while MVPA minutes fell from 28 to 22 per day after people began a GLP-1 receptor agonist medication.
Crucially, the study found no evidence that weight loss from these medications led to increased physical activity. The expected rebound in movement simply did not appear in the data.
Who saw the biggest changes
The decline was not evenly spread. The largest drops were seen in men and in people living with joint or muscle pain. By contrast, factors such as age, heart failure or a prior stroke did not change the results, suggesting the pattern held across a fairly broad range of circumstances.
Why activity cannot be an afterthought
For Dr Maharjan, the practical message is that exercise needs to be designed into treatment rather than left to chance:
“While many assume that weight loss leads naturally to increased physical activity, our study suggests otherwise. The findings in our study reinforce that exercise cannot be optional for people taking these medications. People need targeted interventions that encourage physical activity alongside medication for obesity.”
Given that GLP-1 receptor agonists reduce lean muscle alongside fat, a fall in activity could compound the loss of strength, making structured support for movement an important part of care rather than a nice-to-have.
A first for wearable-data research
The study stands out for its method as much as its findings. It is the first large study analysing data from wearable fitness trackers among adults taking GLP-1 receptor agonists, offering a more objective window into everyday behaviour than questionnaires alone can provide. As these medications become more widely used, that kind of real-world evidence is likely to shape how clinicians and patients approach physical activity during treatment.
CCH insights:
This is a very interesting study, but it throws up more questions than answers. Firstly, were any of the participants receiving diet and lifestyle advice as they are supposed to? GLP-1 medications are designed as an adjunct to such advice, but these results suggest it was probably lacking from these patients’ treatment. Another question, of course, is why did physical activity drop? Further research is needed to understand what is the underlying reason for these results. But most importantly, this study is a reminder that GLP-1 therapy is not just about taking the medication, it requires diet and lifestyle advice and ongoing support and monitoring.
Source: Endocrine Society
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New Triple-Hormone Injection Shows Major Weight Loss in People with Type 2 Diabetes and Obesity
Key Takeaways:
- In a phase 3 trial, retatrutide cut body weight more than four times as much as placebo and roughly doubled the reduction in long-term blood sugar.
- The once-weekly jab works through three hormone pathways at once – GLP-1, GIP and glucagon – the last of which may help raise energy expenditure.
- Experts called the results encouraging but stressed that head-to-head trials against existing drugs are still needed.
A new approach to managing type 2 diabetes
A once-weekly injection that works through three hormone pathways at the same time could deliver substantial reductions in both blood sugar and body weight for people with type 2 diabetes, according to phase 3 trial results.
People taking part in the trial who received weekly retatrutide injections over 40 weeks lost more than four times as much weight as those given a placebo, while their average reduction in long-term blood sugar (HbA1c) was more than twice that seen in the placebo group.
How retatrutide works
Retatrutide is described as a triple-hormone drug because it mimics three gut hormones that help regulate appetite, blood sugar and metabolism: GLP-1, GIP and glucagon.
This sets it apart from several medications already in use. Drugs such as Ozempic and Wegovy primarily target the GLP-1 pathway to suppress appetite, while Mounjaro combines GLP-1 with GIP to help control blood-sugar levels. Retatrutide goes a step further by also engaging the glucagon receptor, which is thought to help increase energy expenditure.
Inside the phase 3 trial
The trial, published in the Lancet, randomly assigned 930 adults with type 2 diabetes to receive either 4mg, 9mg or 12mg of retatrutide, or a placebo.
None of the participants were already taking diabetes medicines. All had inadequately controlled blood-sugar levels and a body mass index (BMI) of at least 23.
Throughout the trial, researchers monitored a range of health markers, including HbA1c, weight, cholesterol levels and other indicators, and recorded any side-effects that arose.
What the results showed
After 40 weeks, participants receiving retatrutide saw their HbA1c fall by an average of about 1.7–1.9 percentage points, compared with 0.8 in the placebo group.
The weight loss results were similarly marked. On average, participants taking retatrutide lost about 11.5%–15.3% of their body weight, against 2.6% for those on placebo. Cholesterol and blood pressure also improved among people taking the drug.
Safety and side-effects
Fourteen participants experienced serious adverse events during the trial, including two in the placebo group. For most people, however, side-effects were mild to moderate and eased over time, with gastrointestinal symptoms the most commonly reported.
What the findings could mean
The study authors say this triple-action medication has the potential to improve health outcomes for some people, including greater weight loss, particularly for those who may need more intensive treatment regimens to manage their type 2 diabetes. Further clinical trials are continuing.
The results follow earlier findings from the manufacturer, Eli Lilly, which suggested that retatrutide was highly effective at reducing weight among people with obesity.
What the experts say
Dr Kath McCullough, special adviser on obesity at the Royal College of Physicians, said the findings were very encouraging.
“For many people living with diabetes and obesity, treatments like this could be genuinely life-changing,” she said.
“However, medications are not a silver bullet. While they are proving to be effective, the long-term goal must be to prevent people from needing them in the first place.”
Dr Marie Spreckley, a specialist in prevention of diabetes and related metabolic disorders at IMS Epidemiology, University of Cambridge, said the results were striking: “The magnitude of weight loss observed is particularly notable. However, because this study compared retatrutide with placebo rather than semaglutide or tirzepatide, it is not possible to determine from this data whether retatrutide is superior, equivalent or inferior to currently available therapies. Direct head-to-head trials will be required before firm conclusions can be drawn regarding comparative effectiveness.”
She added that weight loss alone did not necessarily equate to optimal health outcomes, and that people needed support to maintain adequate nutritional intake, preserve muscle mass and maximise long-term health during treatment.
Dr Lucy Chambers, the head of research impact and communications at Diabetes UK, said: “These encouraging findings show that this new class of drug for type 2 diabetes could deliver dual benefits for both weight loss and blood-sugar management. We look forward to further research to understand its long-term effects and how it compares to treatments already available on the NHS.”
Source: The Guardian
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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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