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.
CCH insights:
This study suggests most patients see GLP-1 medications as a temporary treatment to lose weight, rather than a long-term treatment for obesity and cardiometabolic health. It also suggests patients are not getting good advice regarding GLP-1 therapy. In the long-term, patients should be advised to reduce down to the minimum dose that enables them to maintain weight loss and also maintain gains in metabolic markers and improvements in cardiovascular risk factors, rather than stopping and restarting treatment.
Getting that judgement right – knowing when to hold a dose, when to step down rather than stop, how to keep a patient nourished when side effects bite, and how to prepare them for the long term – is exactly what our two-hour CPD course GLP-1RAs in Practice: Supporting Patients During Treatment is built around, for any clinician supporting patients across the full arc of therapy.
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.
CCH insights:
This was a very small scale pilot study, so we can’t draw any conclusions, but it is an important step towards developing tests or measurements that can improve the personalisation of obesity care and improve the efficiency and effectiveness of obesity treatment.
Making sense of early findings like these – and understanding the incretin physiology that explains why semaglutide and tirzepatide can behave so differently from one patient to the next – is exactly what our two-hour CPD course GLP-1RAs in Focus – Why Drugs Like Ozempic Work is built for, giving any clinician the grounding to weigh new GLP-1RA evidence on its merits rather than its headlines.
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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.”
Keeping pace with this fast-evolving mechanistic understanding of anti-obesity medications is the focus of professional training such as the College of Contemporary Health’s GLP-1RAs in Focus, a CPD-accredited online short course that grounds clinicians in how these drugs work.
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.
CCH insights:
This is a fascinating study. For many years researchers have been looking at ways to stimulate brown adipose tissue (BAT) activity, or enhance beige adipose tissue production, without much success, except for asking people to spend hours in the cold every day. Now it seems we may have stumbled across an answer by accident. The question now is, how does tirzepatide have this effect, and could we develop other agents which act in a similar way to activate BAT and beige adipose tissue without affecting gastro-intestinal function and/or appetite? This would enable us to widen the range of tools for obesity care.
Following where questions like this lead – how a dual GIP/GLP-1 agent acts on energy expenditure and not just appetite – starts with a solid grounding in the underlying physiology, which is exactly what our two-hour CPD course GLP-1RAs in Focus – Why Drugs Like Ozempic Work is built to give any clinician wanting to understand these medications at the mechanistic level wanting to understand these medications at the mechanistic level.
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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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Beyond the Scales: Why Physical Activity Remains Central to Obesity Care
Key Takeaways:
- Exercise earns its place in obesity care through benefits the scales never show – lower blood pressure, better insulin sensitivity and improved fitness – so it remains worthwhile even when weight changes little.
- On its own, activity shifts the scales only modestly, but paired with diet, obesity medications or surgery it protects lean muscle, drives fat loss and makes the results last.
- Tools such as the 5A consultation model, wearables and app-based coaching can lift adherence, though their value depends on access, accuracy and how well they fit each person’s life.
How much weight someone loses has long been the headline measure of whether obesity treatment is working. A new scientific statement from the American Heart Association, published in Circulation, makes the case that this measure misses much of what physical activity actually does. Movement, the statement argues, reshapes cardiovascular and metabolic health in ways that a set of weighing scales will never register.
What activity does that the scales cannot capture
Obesity sits at the centre of cardiovascular risk because of the company it keeps: raised blood pressure, disordered blood fats and insulin resistance. With roughly 42% of adults in the United States affected, the stakes are considerable, and treatment has traditionally pursued two linked aims, shedding weight and lowering heart disease risk.
Physical activity contributes to both, but the more interesting finding is how much it achieves on its own terms. Regular exercise lowers blood pressure, sharpens the body’s response to insulin and nudges cholesterol and other lipids in a healthier direction, and it does so whether or not the number on the scales falls. Aerobic and resistance training each deliver. As a rough rule, doing more tends to help weight-related outcomes most, while working harder pays off most for cardiorespiratory fitness.
Why exercise alone is a poor weight-loss strategy
If the goal is purely to lose weight, activity by itself is an inefficient route. Unless someone trains at high volumes, the losses are usually small, and fewer than one person in seven manages a clinically meaningful reduction through exercise alone. The body, in effect, fights back: appetite climbs and metabolism slows, eroding the deficit that training creates.
This is why exercise works best in combination. Adding it to a calorie-reduced diet produces more weight loss and better metabolic results than either approach in isolation. And the composition of that loss matters as much as the total. Eating enough protein and including resistance work helps ensure the weight that goes is fat rather than muscle, preserving the lean tissue that keeps metabolism and strength intact.
Keeping weight off is the harder battle
Losing weight is difficult; not regaining it is harder still, and regain tends to undo the health gains that came with it. Here the evidence points firmly towards higher activity levels, somewhere between 200 and 300 minutes a week, as a marker of people who keep weight off successfully. The catch is that few people sustain that volume.
A more realistic path is to build gradually towards at least 150 minutes a week of moderate-to-vigorous activity, then add more where possible. Even when some weight creeps back, staying active keeps the cardiometabolic benefits in play, which is reason enough to maintain the habit rather than abandon it after a setback.
Where medication and surgery enter the picture
For people whose body mass index is high and for whom lifestyle change has not been enough, obesity medications and bariatric surgery are central options. Both are effective, and both come with real-world limits around cost, availability and side effects. Neither replaces an active lifestyle; the statement frames physical activity as the strategy that should run alongside them.
The newer GLP-1 receptor agonists, including liraglutide, semaglutide and tirzepatide, have transformed what medication can achieve, with some trials approaching the results once seen only after surgery. They work mainly by curbing appetite and slowing the stomach’s emptying, and although side effects are common, they are usually manageable. Beyond weight, liraglutide and semaglutide have been shown to cut major cardiovascular events in certain high-risk groups.
What remains poorly understood is how exercise fits into this newer landscape. Most medication trials simply have not isolated what activity adds, or how the two interact, leaving the ideal exercise prescription for people on these drugs an open question. The issue is sharpened by the fact that a notable share of the weight lost on GLP-1 receptor agonists is lean tissue rather than fat, even if the long-term consequences of that are not yet clear. The handful of studies that do compare medication with and without exercise suggest that adding activity means more fat loss and better fitness, but the field is still waiting for the large, controlled trials that would settle the matter.
Surgery raises related questions. People approaching bariatric procedures tend to be less active to begin with, and there is no agreed playbook for the period beforehand; insurer-mandated pre-surgical activity programmes exist, but the evidence that they change outcomes is thin and inconsistent. Afterwards, the picture is clearer: people who move more lose more weight and fat, hold onto those losses, and gain in fitness and strength, though effects on metabolic risk markers vary and access to structured programmes is frequently lacking.
Turning good intentions into sustained habits
Clinicians are not bystanders in any of this. A widely used framework, the 5A model, gives consultations a useful spine: assess where the person is, advise on the options, agree on goals, assist in pursuing them and arrange follow-up. Worked through properly, each step tends to deepen engagement with both dietary change and activity, making healthy behaviours easier to stick to.
Doing this well means looking past activity levels alone to the psychological, social and medical factors that can stall progress, and gauging how ready and confident someone feels about changing. Counselling tailored to that profile builds motivation and trust, which in turn supports the activity itself. Equipping clinicians to weave physical activity, dietary change and behaviour change into everyday obesity consultations is the focus of practical training such as the College of Contemporary Health’s Obesity Toolbox, a CPD-accredited online short course. Because a short appointment can only do so much, part of the clinician’s job is helping people spot the obstacles in their way, solve them together, and connect with wider support, whether behavioural counselling or a digital programme that keeps them accountable between visits.
Technology is increasingly part of that support. Wearables, apps, text reminders, personalised feedback and self-monitoring all show promise for keeping people moving. The statement is careful, though, to flag the caveats: not everyone has equal access to these tools, the devices vary in how accurately they measure activity, and none of it substitutes for regular reassessment and structured follow-up.
The bottom line for treatment
Physical activity belongs at the heart of comprehensive obesity care, supporting weight loss, helping maintain it and improving health more broadly. Medications and surgery are genuine advances, but exercise adds something they do not fully provide: gains in cardiovascular risk, body composition, fitness and quality of life, many of which arrive independently of any change on the scales.
Delivering that well takes teamwork across clinicians and allied health professionals, and programmes that are not only effective but also affordable and within reach, especially for under-resourced communities where obesity is more common and activity levels lower. Making the wider case for movement, rather than treating it as a weight-loss tool alone, is likely to be what makes obesity treatment hold up over the long run and eases the cardiovascular toll that obesity exacts.
CCH insights:
This study strikes right at the heart of how our understanding of obesity is starting to change – it is not all about body weight and body fat, but about health. Although reducing harmful body fat is an important part of obesity treatment, so is improving cardiometabolic health and other health issues that arise as a result of obesity. And physical activity is a vital tool in delivering these health improvements – helping to reduce blood pressure, regulate blood glucose, reduce cholesterol and improve
muscle mass and function – whether or not it results in weight loss whether or not it results in weight loss. For clinicians looking to put this into practice, CCH’s Obesity Toolbox (1.5 hours, fully online, CPD-accredited) is a quick, practical primer on the essentials of physical activity, dietary change and behaviour change in obesity care – a fast starting point for busy practitioners.
Explore the Obesity Toolbox →
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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