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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.

Explore GLP-1RAs in Focus →

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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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 →

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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).

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Bariatric Surgery Delivers Greater Weight Loss and Disease Remission Than GLP-1 Drugs, Large Analysis Finds

Key Takeaways:

• A large real-world analysis involving more than 430,000 patients found that metabolic and bariatric surgery produced substantially greater weight loss than GLP-1 medications after 12 months.
  
• Surgery was associated with higher remission rates for obesity-related conditions including type 2 diabetes, hypertension and high cholesterol.
  
• Researchers and clinicians said GLP-1 medications represent an important advance in obesity care, but cautioned that they should not be viewed as a replacement for metabolic and bariatric surgery in people requiring more substantial and durable outcomes. 
  
  
  

Surgery outperformed GLP-1 drugs across key outcomes

Metabolic and bariatric surgery may provide significantly greater weight loss and higher rates of obesity-related disease remission than glucagon-like peptide-1 receptor agonist medications, according to a major new real-world comparison presented at the American Society for Metabolic and Bariatric Surgery (ASMBS) Annual Meeting 2026.

The systematic review and analysis, described as one of the largest and most comprehensive comparisons of the two treatment approaches to date, evaluated data from 30 clinical studies involving more than 430,000 patients. Researchers found that although both treatments produced meaningful clinical benefits for people living with obesity, metabolic and bariatric surgery consistently outperformed GLP-1 therapies across all major outcomes assessed.

The research was conducted by investigators from Yale School of Medicine, Coreva-Scientific, Vanderbilt University and UT Health San Antonio.

Greater weight loss after surgery

According to the findings, people who underwent metabolic and bariatric surgery experienced more than 20% greater weight loss at 12 months compared with those treated with GLP-1 receptor agonist medications.

Researchers also reported that surgery was linked to substantially higher remission rates for several obesity-related health conditions. Compared with GLP-1 therapy, metabolic and bariatric surgery was associated with:

• 42% higher remission rates for type 2 diabetes
• 12.8% higher remission rates for hypertension
• 20.8% higher remission rates for high cholesterol

The analysis focused specifically on studies that directly compared bariatric surgery with GLP-1 receptor agonists. Studies that combined surgery and medication therapies were excluded from the review.

The primary endpoint examined was weight loss at 12 months. Secondary endpoints included remission of obesity-related conditions such as type 2 diabetes, hypertension and hyperlipidaemia.

Researchers highlight durability of surgical outcomes

The study authors noted that although GLP-1 medications have transformed obesity treatment and expanded evidence-based care options, metabolic and bariatric surgery continues to deliver greater and more durable results for many patients.

“While GLP-1 medications are an important advance, they do not match the magnitude or durability of outcomes achieved with metabolic and bariatric surgery, which remains one of the most underutilized treatments in medicine. Once the medications are discontinued, whether due to side effects, cost or other factors, their benefits often diminish or disappear, whereas the benefits of surgery endure.” – John M. Morton, MD, MPH, FASMBS, Study Co-Author, Professor of Surgery and Vice-Chair, Quality, Surgery at Yale School of Medicine

The findings add to ongoing discussions within obesity care about how best to position GLP-1 therapies and surgical interventions within long-term treatment pathways.

Evidence gap in direct comparisons

Despite the rapid growth in the use of GLP-1 medications such as semaglutide and tirzepatide, researchers noted that direct comparisons between these drugs and bariatric surgery remain limited.

The review involved a comprehensive search of PubMed and EMBASE databases to identify relevant studies comparing the two treatment approaches.

Commenting on the findings, an independent obesity surgery expert said the analysis helps address a major evidence gap in the field.

“Despite the explosive growth of GLP-1 drugs, no randomized controlled trials have directly compared them to bariatric surgery. This analysis helps fill that evidence gap,” said John Scott, MD, FACS, FASMBS, clinical professor of surgery at the University of South Carolina School of Medicine Greenville and metabolic and bariatric surgery director for Prisma Health, who was not involved in the study.

“GLP-1s have expanded evidence-based treatment options, but they should not be seen as a replacement for surgery – especially for patients who require the level of outcomes that only metabolic and bariatric surgery can provide.”

Expanding treatment options in obesity care

The findings come amid growing global interest in obesity treatment strategies as the use of GLP-1 receptor agonists continues to rise rapidly. Medications in this class have demonstrated significant effectiveness for weight reduction and metabolic health improvement, but concerns remain regarding long-term adherence, cost, side effects and weight regain after discontinuation.

Metabolic and bariatric surgery, meanwhile, has long been associated with substantial and sustained weight loss as well as improvements in obesity-related conditions such as type 2 diabetes and cardiovascular risk factors. However, experts have repeatedly argued that surgery remains significantly underutilised despite its established effectiveness.

The researchers concluded that while both treatment approaches play an important role in obesity management, metabolic and bariatric surgery continues to provide the most substantial improvements in weight loss and disease remission outcomes based on current comparative evidence.

Source: American Society for Metabolic and Bariatric Surgery

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People Judge Weight Loss More Harshly When GLP-1 Drugs Are Used, Study Finds

Key Takeaways:

• People using GLP-1 and other anti-obesity medications were consistently judged more negatively than those losing weight through diet and exercise alone.
  
• Researchers found that anti-obesity medication users were perceived as putting in less effort and were therefore viewed as less moral, competent, warm, and deserving of their success.
  
• The findings suggest that stigma surrounding obesity treatment may discourage people from seeking effective medical care and reinforce harmful misconceptions about obesity and weight loss.
  
  
  

Study explores social attitudes toward weight loss medication

A recent study published in Scientific Reports has found that people who lose weight using anti-obesity medications (AOMs), including glucagon-like peptide-1 (GLP-1) receptor agonists, are often judged more harshly than those who lose weight through diet and exercise alone.

The research examined how the use of anti-obesity medication influences perceptions of effort, morality, competence, warmth, and deservingness. The findings suggest that social attitudes toward obesity treatment remain strongly shaped by beliefs about personal effort and self-control.

With more than one billion people worldwide living with obesity, the researchers noted that how a person loses weight can significantly influence how others perceive them. Although GLP-1 receptor agonists and other anti-obesity medications have demonstrated substantial effectiveness in treating obesity, they are frequently criticised as an “easy way out.”

According to the researchers, this perception reflects a broader psychological phenomenon known as effort moralization – the tendency to associate greater effort with greater moral worth.

The authors explained that such beliefs may reinforce obesity stigma, discourage people from seeking treatment, and negatively affect both physical and mental health outcomes.

While anti-obesity medications can provide important medical support for people living with persistent obesity, the researchers stressed that understanding the social impact of these perceptions is necessary if the full potential of these treatments is to be realised.

Four studies conducted across three countries

The research involved four pre-registered experimental studies conducted between November 2024 and February 2025 in Belgium, the United States, and the United Kingdom.

In total, 1,205 participants took part in the research. Participants were recruited online through university participant pools and the Prolific platform. Researchers applied several quality-control measures, excluding incomplete responses, failed attention checks, overly rapid responses, and participants with insufficient language proficiency.

Across the studies, participants were presented with descriptions of two individuals who shared identical weight-loss goals and similar experiences with diet and exercise. The only difference between the individuals was that one used an anti-obesity medication while the other did not.

Participants then rated both individuals using Likert-type scales assessing:

• Perceived effort
• Moral character
• Warmth
• Competence
• Deservingness of weight-loss success
• Willingness to cooperate with them in future scenarios

The researchers also explored several additional variables across the studies, including:

• General attitudes toward anti-obesity medication
• Personal or social experience with weight-loss medication
• Beliefs that anti-obesity medication represents a “shortcut”
• Personality traits measured using the Big Five Inventory (BFI)

To analyse the data, the researchers used t-tests, correlations, multilevel modelling, and evidence synthesis techniques.

Anti-obesity medication users viewed more negatively

Across all four studies, the findings revealed a consistent pattern of negative social judgement toward individuals using anti-obesity medication.

Compared with people relying solely on diet and exercise, anti-obesity medication users were perceived as putting in less effort into achieving their weight-loss goals.

This perception of lower effort was strongly linked to harsher moral evaluations. Participants consistently rated anti-obesity medication users as less moral than non-users.

In Study 1, for example, significantly lower perceived effort ratings for anti-obesity medication users were accompanied by similarly large reductions in moral character ratings.

The bias extended beyond morality alone.

Participants also viewed anti-obesity medication users as:

• Less competent
• Less warm
• Less deserving of their success

In addition, participants reported lower anticipated satisfaction with future cooperation involving anti-obesity medication users in a hypothetical training-partner scenario.

According to the paper’s evidence synthesis, most of these effects were large, although the effect relating to warmth was more moderate.

Perceived effort was closely tied to moral judgement

One of the most significant findings was the strong relationship between perceived effort and moral judgement.

Across all four studies, larger differences in perceived effort between medication users and non-users were associated with larger differences in moral evaluations.

The researchers concluded that perceptions of effort appear to play a major role in shaping broader social judgement.

The findings support the idea that many people continue to associate moral worth with visible personal struggle and self-discipline, particularly in relation to body weight and weight loss.

“Shortcut” beliefs intensified negative bias

The study also examined factors that influenced the strength of these perceptions.

Participants who held more positive views toward anti-obesity medications, or who had prior personal or social experience with such treatments, tended to judge medication users less harshly.

In contrast, stronger beliefs that anti-obesity medication represents a “shortcut” to weight loss were associated with more negative moral judgements.

In some analyses, these shortcut beliefs also amplified the relationship between perceived effort and bias.

The researchers found that personality traits such as conscientiousness and extraversion had little overall effect on participants’ judgements. This suggests that the bias is driven more by beliefs about effort and treatment legitimacy than by broader personality characteristics.

One exploratory analysis identified a small association with neuroticism, although this effect was limited.

Meta-analytic evidence synthesis across the studies confirmed that most effects were large, particularly for:

• Perceived effort
• Moral judgement
• Competence
• Cooperation satisfaction
• Deservingness

Effects relating to warmth were moderate by comparison.

Findings highlight social challenges surrounding obesity treatment

The researchers concluded that using anti-obesity medication is not simply a medical decision, but also a social one that may expose individuals to stigma and negative judgement.

According to the findings, people using anti-obesity medications are frequently perceived as putting in less effort and are therefore judged as less moral, less competent, and less deserving of success.

Although the studies were based on vignette scenarios rather than real-world interactions, the researchers stated that the findings point toward a widespread bias rooted in effort moralization.

They suggested that these attitudes could influence interpersonal relationships, healthcare experiences, and broader public perceptions of obesity treatment.

The authors argued that addressing these misconceptions is important for improving healthcare quality and reducing obesity-related stigma.

They also suggested that public education and changes in the way weight loss is discussed may help shift attention away from perceived effort and toward health outcomes and overall well-being.

CCH insights:

Unfortunately, this shows that there is still a very poor understanding of obesity amongst the general public, which means that biased, negative attitudes towards people with excess weight persist. Instead of being seen as medical tools to treat a complex chronic condition, GLP-1 medications are seen by many as short-cut for weight loss cheats. Current evidence suggests these attitudes are common even within the health professions. To improve the quality of obesity care, and to encourage those who need help to seek it, these misconceptions must be addressed.

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Adding Weekly GLP-1 to CBT Further Reduces Heavy Drinking

Key Takeaways:

• A new randomised controlled trial found that weekly semaglutide injections combined with cognitive behavioural therapy significantly reduced heavy drinking days in people living with obesity and alcohol use disorder.
  
• Participants receiving semaglutide experienced a 41.1% reduction in heavy drinking days, which was notably greater than the reduction seen in the placebo group.
  
• Researchers say the findings add to growing evidence that GLP-1 receptor agonists may have therapeutic potential beyond weight management, including in the treatment of substance use disorders.
  
  
  

Study suggests GLP-1 therapy may help address alcohol use disorder

A team of researchers from the National Institutes of Health (NIH), Copenhagen University Hospital, and international collaborators has reported the first evidence from a randomised controlled clinical trial showing that a GLP-1 receptor agonist may help reduce heavy drinking in people living with both obesity and alcohol use disorder.

The findings, led by researchers at Copenhagen University Hospital, contribute to a growing body of research suggesting that GLP-1 receptor agonists such as semaglutide may have applications beyond obesity and type 2 diabetes treatment, including potential use in substance use disorders.

Alcohol use disorder remains significantly undertreated worldwide, despite its substantial impact on physical health, mental health, and mortality. Current pharmacological treatment options are limited and often underused in clinical practice.

“Very few medications are currently approved for alcohol use disorder, and these are vastly underutilized. A new option that is more accessible and more effective could be a gamechanger for closing the treatment gap,” said Director of NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA) George Koob, Ph.D., a study co-author.

Increasing interest in GLP-1s for addiction and substance use disorders

In recent years, researchers have become increasingly interested in the possible role of GLP-1 receptor agonists in addiction medicine.

GLP-1 drugs were originally developed for type 2 diabetes and later became widely used for obesity management due to their effects on appetite regulation, satiety, and weight reduction. However, emerging research has suggested these medications may also influence the brain’s reward pathways and reduce cravings or compulsive behaviours associated with substance use disorders.

Previous studies examining GLP-1 therapies in alcohol use disorder have produced mixed findings. One recent clinical trial found that a GLP-1 receptor agonist did not significantly reduce heavy drinking across the entire study population. However, researchers observed that participants living with obesity appeared to respond particularly well.

The latest study was designed specifically to investigate this subgroup.

Trial focused on people living with both obesity and alcohol use disorder

The research team enrolled 108 treatment-seeking adults living with alcohol use disorder and comorbid obesity.

All participants received standard cognitive behavioural therapy (CBT), which is a commonly used psychological treatment for alcohol use disorder that aims to help people identify and modify harmful thought patterns and behaviours associated with drinking.

Participants were then randomly assigned to receive either:

• Weekly semaglutide injections
• A placebo injection

The intervention lasted for 26 weeks.

Throughout the study period, researchers collected self-reported alcohol consumption data and monitored several quantitative biomarkers associated with alcohol use. These biological measurements were used to support and validate the participants’ reported drinking behaviour.

Semaglutide group experienced larger reduction in heavy drinking

At the end of the study, the researchers found that participants receiving semaglutide experienced a substantial decline in heavy drinking days.

According to the findings:

• The semaglutide group showed a 41.1% reduction in heavy drinking days
• This represented a 13.7% greater reduction compared with the placebo group

Importantly, biomarker data measuring alcohol exposure supported the self-reported reductions in drinking behaviour, strengthening confidence in the results.

Researchers also observed improvements in several cardiometabolic measures among participants receiving semaglutide. As expected based on previous obesity trials, reductions in body weight and blood pressure were more pronounced in the GLP-1 treatment group.

Researchers note mild and temporary side effects

The study authors reported that semaglutide was generally well tolerated.

Some participants experienced adverse effects, primarily gastrointestinal symptoms, which are commonly associated with GLP-1 receptor agonists. However, the researchers noted that these symptoms were generally mild and transient.

No unexpected safety concerns were highlighted in the report.

Potential clinical impact compared with existing medications

The investigators also evaluated the treatment’s number needed to treat (NNT), a standard clinical metric used to estimate how many people need to receive a treatment for one person to benefit.

In this study, semaglutide achieved an NNT of 4.3.

The researchers noted that currently approved medications for alcohol use disorder typically have an NNT of 7 or higher, suggesting semaglutide may potentially produce clinically meaningful benefits more frequently than existing therapies.

While the authors stressed that further research is needed before definitive conclusions can be drawn, the findings are likely to increase interest in GLP-1 therapies as a possible future treatment option for alcohol use disorder.

“We’re beginning to see some of that potential for GLP-1s to treat drug addiction turn into reality. Questions remain but this is nonetheless very encouraging,” said Director of NIH’s National Institute on Drug Abuse (NIDA) and study co-author Nora Volkow, M.D.

Larger and longer studies still needed

Despite the encouraging findings, the researchers emphasised that additional studies will be necessary to confirm the results.

Future research will need to assess:

• Whether the effects persist over longer periods
• How GLP-1 therapies perform in larger and more diverse populations
• Which patient groups are most likely to benefit
• Whether similar effects are seen in people without obesity

The authors stated that they hope to examine the effects of GLP-1 receptor agonists over a longer duration and in larger study populations in future investigations.

The scientific team was led by first author Mette Kruse Klausen, M.D., and corresponding author Anders Fink-Jensen, D.M.Sc., at Copenhagen University Hospital.

CCH insights:

These results are very promising, suggesting GLP-1 medications offer an effective treatment option for some people with obesity and alcohol use disorder (AUD). However, these patients would need careful monitoring in terms of diet and nutrition. People with AUD are susceptible to nutrient deficiencies because they get most of their calories from alcoholic drinks. If they eat less than usual due to appetite suppression induced by GLP-1 therapy, there is a risk of exacerbating these deficiencies. 

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New Study Suggests Semaglutide May Reduce Epilepsy Risk in Adults with Type 2 Diabetes

Key Takeaways: 

• Initiating semaglutide was associated with a significantly lower risk of developing epilepsy or seizures compared with other glucose-lowering therapies.
  
• The observed effect does not appear to be primarily driven by improvements in blood glucose or body weight.
  
• Findings are preliminary and should be interpreted as an early signal rather than a basis for changing clinical practice.
  
  
  

Background – seizure risk in type 2 diabetes

People living with type 2 diabetes mellitus face a higher risk of developing seizures and epilepsy. This increased risk is thought to be partly driven by inflammatory processes that affect the central nervous system. While glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are primarily used for glucose regulation, there has been growing scientific interest in their potential neurological effects.

However, until now, the relationship between GLP-1 RAs and seizure risk has remained unclear.

Study design and population

The findings were presented at the American Academy of Neurology Annual Meeting, held in Chicago from April 18 to 22, 2026.

Researchers conducted a retrospective study using a target trial emulation approach, drawing on data from the National Institutes of Health All of Us Controlled Tier Dataset. The analysis focused on adults aged 18 years and older with type 2 diabetes mellitus who initiated one of the following treatments between December 2018 and December 2021:

• Semaglutide
• Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors)
• Other glucose-lowering therapies

Participants were followed through to December 2023.

To ensure comparability between groups, inverse probability of treatment weighting was applied to balance baseline characteristics. Time-to-event analyses were then used to assess the risk of developing epilepsy or seizures.

Cohort characteristics

A total of 393,596 individuals met eligibility criteria. Within this population:

• 8,533 individuals were included in the semaglutide versus other glucose-lowering drug comparison (2,397 vs 6,136)
• 7,455 individuals were included in the semaglutide versus SGLT2 inhibitor comparison (1,650 vs 3,725)
  
  
  

Key findings – reduced risk of seizures

After statistical adjustment, initiation of semaglutide was associated with a lower risk of epilepsy or seizures compared with both comparator groups:

• Compared with other glucose-lowering drugs:
  • Hazard ratio: 0.46
  • 95% confidence interval: 0.25–0.83
  • P = .010
• Compared with SGLT2 inhibitors:
  • Hazard ratio: 0.44
  • 95% confidence interval: 0.22–0.86
  • P = .017

These findings suggest a meaningful reduction in relative risk among those initiating semaglutide.

Absolute risk reduction and clinical interpretation

Further modelling provided estimates of absolute risk reduction:

• Compared with other glucose-lowering therapies:
  • Absolute risk reduction: -0.014
  • Number needed to treat: 69
  • P < .001
• Compared with SGLT2 inhibitors:
  • Absolute risk reduction: -0.008
  • Number needed to treat: 129
  • P < .001

These results indicate that, while the relative risk reduction is notable, the absolute reduction in risk remains modest.

Mechanisms – not driven by glycaemic control alone

To explore potential mechanisms, the researchers conducted mediation analyses. These analyses assessed how much of the observed effect could be explained by changes in glycated haemoglobin or body mass index.

The results showed that:

• Glycated haemoglobin accounted for only 1.1% of the effect compared with other glucose-lowering drugs and 3.6% compared with SGLT2 inhibitors
• Body mass index contributed 0.3% or less in both comparisons

This suggests that the reduced seizure risk may not be primarily driven by improvements in glycaemic control or weight loss, pointing towards other possible mechanisms.

Expert perspective

Yoonhyuk Jang, MD, PhD, Postdoctoral Fellow in the Department of Immunology at Harvard Medical School, commented on the findings:

“This study suggests that semaglutide may be associated with a lower risk of adult-onset seizures or epilepsy in patients with type 2 diabetes, with the signal appearing more pronounced in late-onset cases among adults aged 60 years or older.”

He added:

“Given that age-associated brain insults are major contributors to adult-onset seizures and epilepsy, these findings may have implications beyond seizure risk alone and raise the possibility that semaglutide could also be relevant to broader brain health; however, because this was a retrospective target trial emulation with a relatively small number of events, it is not yet practice-changing and should instead be viewed as a signal that supports further research into the role of GLP-1 receptor agonists in epileptogenesis.”

Limitations and future directions

The authors emphasised that the study design was observational, despite using advanced statistical methods to emulate a clinical trial. As such, causality cannot be definitively established.

Additionally, the relatively small number of seizure events limits the strength of the conclusions. These findings should therefore be interpreted cautiously and seen as hypothesis-generating.

Further prospective and randomised studies will be needed to determine whether GLP-1 receptor agonists such as semaglutide have a direct role in reducing seizure risk or influencing broader neurological health.

Disclosures

One study author reported affiliations with biotechnology, pharmaceutical, or device companies. Full disclosure details are available in the original study source.

Source: Neurology Advisor

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Can Less Be More? Reduced GLP-1 Dosing May Sustain – and Even Enhance – Weight Loss

Key Takeaways: 

• Structured reduction in GLP-1 receptor agonist dosing frequency may allow continued weight loss while lowering treatment burden
  
• Cardiometabolic improvements achieved during weekly dosing appear to be maintained with less frequent dosing
  
• Early evidence suggests some individuals may not require high or frequent dosing to sustain weight loss, although larger trials are needed
  
  
  

A new approach to GLP-1 treatment

Emerging evidence suggests that reducing the frequency of glucagon-like peptide-1 receptor agonist (GLP-1 RA) dosing may still deliver sustained benefits for people living with obesity. Data presented at the Obesity Medicine Association’s annual conference indicate that a structured, gradual de-escalation strategy could maintain, and in some cases enhance, weight loss outcomes while reducing the burden of ongoing treatment.

This finding challenges the prevailing assumption that continuous, high-frequency dosing is required to preserve the benefits of these therapies.

Continued weight loss despite reduced dosing

The research, led by Mitch Biermann, MD, PhD, examined outcomes in individuals who transitioned from weekly GLP-1 RA dosing to less frequent schedules. Reflecting on the results, Biermann noted:

“What I found was actually surprising, where in addition to losing weight initially on the weekly regimen, people actually lost further weight on the every-other-week regimen,” Mitch Biermann, MD, PhD, an obesity medicine physician and scientist at Scripps Health, told Healio. “I was just hoping people would break even, not get an additional 2% weight loss.”

This observation suggests that, for some individuals, reduced dosing frequency does not simply preserve prior weight loss but may contribute to further reductions.

Addressing a common patient concern

The study was partly motivated by a frequent question from patients considering GLP-1 therapy. As Biermann explained:

“The No. 1 question patients have when they’re deciding to start one of these medicines is, ‘Do I have to be on this every week for the rest of my life? Do I have to take this forever?’” he said. “Patients ask that about certain medicines and not others. It usually correlates with the stigma around the disease. They always ask about it for weight loss medicine.”

This highlights an important dimension of obesity care – long-term treatment expectations and the role of stigma in shaping patient concerns.

Study design and patient cohort

The analysis was based on a retrospective case series involving 30 adults who had been prescribed either semaglutide (Wegovy or Ozempic) or tirzepatide (Mounjaro). All participants had experienced a plateau in weight loss during standard weekly treatment.

Participants agreed to reduce their dosing frequency while maintaining their effective dose. The adjusted schedules included:

• Every 10 to 14 days (n = 6)
• Every two weeks (n = 17)
• Longer than every two weeks (n = 7)

The mean follow-up period was 36 weeks.

Body composition and weight outcomes

Following the transition to reduced dosing, participants continued to lose weight, with reported reductions of 72.4 ± 2.2 kg (P < .01). In addition to overall weight loss, improvements were observed in body composition:

• Reductions in body fat mass
• Decreases in average percentage body fat
• Lower truncal fat mass

At the same time, skeletal muscle mass increased slightly from 30.33 ± 1.27 to 30.63 ± 1.25, suggesting that weight loss was not associated with disproportionate muscle loss.

Sustained cardiometabolic benefits

Importantly, key metabolic improvements achieved during weekly dosing were maintained after reducing treatment frequency:

• Glycaemic control: HbA1c improved from 5.6% ± 0.13% before treatment to 5.1% ± 0.1% during weekly dosing (P < .001), with no change during reduced dosing
• Triglycerides: Levels decreased from 121 ± 11.3 mg/dL to 84.3 ± 9.6 mg/dL during weekly dosing (P < .001) and remained stable at 74.8 ± 4.1 mg/dL
• Mean arterial pressure: Reduced from 90.5 ± 2 mm Hg to 84.8 ± 2.1 mm Hg (P < .05), remaining stable at 85.1 ± 1.5 mm Hg during maintenance

The proportion of participants meeting criteria for metabolic syndrome also declined, from nearly 83% before treatment to 68% during weekly dosing and 58.6% following dose reduction.

Interpreting the findings

The study authors suggest that lower levels of GLP-1 receptor stimulation may be sufficient to maintain weight loss once it has been achieved. Biermann offered the following interpretation:

“that you don’t need much of these hormones to maintain weight loss, even though you need a lot of them to reduce weight.”

He also drew a parallel with physical activity:

“Exercise doesn’t cause people to lose a ton of weight. It causes people to maintain their weight if they lose it by another method for the most part,” he said. “And that matches this hormone data, because that 30% increase [in hormone levels] you get on GLP-1s from exercise is probably enough to maintain your weight loss.”

Limitations and considerations

The findings should be interpreted cautiously. The study was small, non-randomised, and based on a retrospective case series. In addition, the cohort lacked diversity, with only four participants not identified as white and just two individuals living with class II or III obesity.

These limitations mean that the results may not be generalisable to broader populations.

Implications for clinical practice

Despite its limitations, the study offers a potentially important insight into long-term obesity management. Gradual dose reduction may represent a viable strategy for some individuals seeking to balance efficacy with treatment burden.

As Biermann concluded:

“I think it’s an option that works for many people, [particularly] when we don’t study how to stop medicine in general,” Biermann told Healio.

“I think it’s nice to have some published data on the average effectiveness of this strategy, even though it’s not a randomized controlled trial,” he said.

Looking ahead

Further research, particularly large-scale randomised controlled trials, will be essential to determine whether reduced dosing strategies can be safely and effectively implemented in routine care. For now, these findings provide an early signal that long-term GLP-1 therapy may not need to follow a one-size-fits-all model.

Source: Healio

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