Obesity Care Tag

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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Childhood Obesity Risk May Begin With Fathers, Long Before Birth

Key Takeaways:

• A review in Current Obesity Reports argues that fathers influence their children’s obesity risk through several interacting biological, behavioural, and environmental pathways that begin before conception – not only through the mother.
  
• Paternal obesity is linked to poorer sperm quality and to epigenetic changes in sperm that can alter gene expression in the developing embryo, although some of these changes appear reversible through lifestyle modification before conception.
  
• The authors call for obesity prevention to include fathers explicitly – through preconceptional counselling, perinatal education for both parents, supportive workplace policies, and more research into the paternal role.
  
  
  

A wider lens on obesity research

A recent review published in the journal Current Obesity Reports suggests that fathers shape their children’s risk of obesity through multiple interacting pathways that begin before conception. The authors argue that efforts to prevent and study childhood obesity should focus on fathers as well as mothers.

Childhood obesity continues to rise in the United States, alongside increasing rates of overweight and obesity among adults. Current projections suggest that more than 250 million Americans could be living with overweight or obesity by 2050.

Research shows that children are more likely to develop obesity when one or both parents are affected, and the risk is highest when both parents have obesity. This pattern reflects the complex interplay of genetic, biological, behavioural, and environmental factors that influence obesity risk across generations.

The Developmental Origins of Health and Disease (DOHaD) framework holds that the periconceptional period is critical in setting the foundation for long-term outcomes, including cardiometabolic disease, through exposure to environmental factors. Maternal nutrition, obesity, and metabolism have been studied in detail because they shape the fetal environment.

More recently, the Paternal Origins of Health and Disease (POHaD) framework has been brought under the DOHaD umbrella. The current review examined the biological, psychological, and behavioural pathways through which paternal factors affect children’s health – though not in isolation from family dynamics and other environmental and social factors. The authors stress that paternal influences operate alongside maternal and broader family influences rather than separately from them.

How obesity alters sperm and offspring metabolism

Around 40% to 70% of obesity is heritable, mediated by hundreds of obesity-linked genetic variants. Obesity in fathers can affect the metabolic health of their offspring through several routes.

Paternal obesity influences sperm quality, reducing sperm concentration and motility and increasing the rate of sperm DNA fragmentation. These changes are linked to the adverse effects of obesity on paternal metabolism. The same sperm abnormalities are reflected in a 30% to 66% increase in the risk of infertility among men with obesity, and they raise the risk of pregnancy loss independently of maternal factors.

Obesity is associated with metabolic dysregulation through disrupted endocrine regulation of sperm production, testicular and systemic inflammation, and epigenetic alterations in sperm. Because sperm cells are produced continuously and mature over several months before conception, there is a wide window during which environmental exposures can leave their mark.

These epigenetic changes are heritable and can affect gene expression in the developing embryo, across pathways tied to appetite regulation, insulin signalling, and fat metabolism. In animal studies, a high-fat diet in the father is associated with obesity-related changes in the offspring. Even so, while animal research provides strong evidence for these mechanisms, the equivalent biological pathways in humans remain incompletely understood.

Notably, some obesity-associated epigenetic changes in sperm appear to be reversible through lifestyle modification before conception.

How a father’s habits shape his child’s behaviours

Becoming a father tends to be associated with weight gain and with changes across multiple health behaviours, for better or worse. A healthy preconceptional paternal diet is associated with improved sperm quality and concentration, regardless of age and body mass index (BMI), while a poor-quality diet has the opposite effect.

The quality of a father’s diet, his physical activity habits, his feeding practices, and his parenting style all influence a child’s eating and activity levels – both directly and indirectly through role modelling. The same applies to a father’s physical activity and sedentary habits.

How neighbourhood and food access shape outcomes

A father’s risk of obesity is influenced by many other factors, including income, education, and neighbourhood type.

The residential neighbourhood affects a child’s diet directly, through food access, and indirectly, through its association with food security, socioeconomic status, and the father’s mental health. Food insecurity is linked to higher consumption of high-calorie foods and an increased risk of obesity. Likewise, limited access to safe recreational spaces restricts physical activity and raises obesity risk.

These factors operate at the family level, touching everything from the father’s physiology and parenting style to the child’s developmental environment. Together they interact to compound the increase in obesity risk across generations.

Mental health is particularly important. A father living with depression is less likely to have an engaged or positive parenting style, or to value preventive healthcare for himself or his family. This can worsen a child’s eating and sleep behaviours and increase obesity risk. Children living with a parent experiencing depression are also at greater risk of adverse childhood experiences (ACEs), which may affect their long-term obesity risk.

Why fathers may shape obesity risk from the start

The authors conclude that fathers play an important role in how obesity risk is transmitted across generations – a process that begins preconceptionally and continues through childhood. They note, however, that much of the current evidence is observational, and that further human research is needed to better understand the biological mechanisms linking paternal health and offspring obesity risk.

They suggest that obesity prevention strategies should include preconceptional counselling that addresses fathers as well as mothers; perinatal education aimed at both parents; the inclusion of fathers in obesity prevention methods; workplace policies that support paternal involvement in childcare; and greater priority for research examining the father’s role in transmitting obesity risk across generations.

CCH insights:

At CCH we have been interested in the mounting evidence around the paternal origins of health and disease (POHaD) for some time, particularly in relation to obesity. This review provides a comprehensive summary of the evidence so far for the important role of fathers, not just in terms of their biological intergenerational impact, but also through health-related behaviours and their influence on the child’s environment.

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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. 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.

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New Research Shows Obesity May Reshape How Breast Cancer Spreads

Key Takeaways:

• Obesity may alter how early, non-invasive breast lesions progress into invasive cancer, a University of Oklahoma study suggests.
  
• In women with obesity, progression was linked to inflammation, immune cell activity, metabolic changes and raised levels of the enzyme SULF2 – not the rapid cell division seen in women without obesity.
  
• The findings could improve risk prediction for women with DCIS and help reduce overtreatment.
  
  
  

A different route to invasive disease

Obesity may change how early-stage breast cancer becomes invasive, according to a study by University of Oklahoma researchers published in The American Journal of Pathology.

Obesity is already recognised as a risk factor for invasive breast cancer, but researchers have not fully understood how it helps early, non-invasive breast lesions develop into invasive cancer. A clearer picture of this process could strengthen physicians’ ability to predict and treat the disease.

In the study, breast cancers in women without obesity displayed the typical signs of turning invasive, including rapid cell division and an increased ability to invade neighbouring tissue. In women with obesity, however, the researchers identified a different set of biological changes that appeared to help the cancer become invasive.

The cancer environment became more inflamed, with the arrival of immune cells that advanced the growth of the tumour. The tumour cells also appeared better able to survive under stress, and there were changes in cellular metabolism – how the cells use nutrients for energy.

“This could be why women with obesity are at higher risk for invasive breast cancer,” said Bethany Hannafon, Ph.D., co-lead author of the study and an assistant professor in the Department of Obstetrics and Gynecology at the OU College of Medicine. “The changes that the cancer cells are undergoing are allowing them to survive and thrive.”

A cooperative cancer “neighbourhood”

The researchers also found differences in the “neighbourhood” of cells and tissues surrounding the cancer. Epithelial cells, where the tumour originally develops, co-opt other cells around them to create an environment that is even more conducive to cancer growth.

“In women with obesity, there is cooperation between all the cell types, not just the cancer cells, which helps an early pre-cancer to become an invasive breast cancer,” said co-lead author Elizabeth Wellberg, Ph.D., assistant professor in the Department of Pathology at the OU College of Medicine. “That may be an area of future study – can a drug or intervention that targets only one cell type interrupt the whole network of progression toward invasive cancer?”

The role of the enzyme SULF2

The research team additionally discovered higher levels of an enzyme called Sulfatase 2 (SULF2) in the tumour cells of women with obesity, suggesting that it may play an important part in cancer progression. SULF2 will be a further focus of future studies.

Why better DCIS risk prediction matters

Understanding what causes early, non-invasive tumours – known as ductal carcinoma in situ, or DCIS – to become invasive is important because not all women will go on to develop invasive cancer, yet they currently receive the same treatment.

“In women diagnosed with DCIS, about half will later develop invasive ductal carcinoma (IDC) that spreads into surrounding breast tissue. But we currently have no way of determining which women are most at risk. As a result, many women with DCIS receive the same treatments used for IDC, including surgery, radiation and sometimes hormone therapy. Overtreatment is a major concern, but if we had better ways of determining risk, unnecessary treatments could potentially be reduced,” Hannafon said.

While breast cancer survival rates have improved over the past two decades, the number of women diagnosed with invasive breast cancer has not declined – underscoring the need for better ways to predict and prevent disease progression.

A growing public health concern

The rising prevalence of obesity gives the findings added weight.

“Obesity is on the rise – 50% of Americans are expected to be obese by 2030,” said the paper’s first author, Cole Hladik, Ph.D., who worked in Hannafon’s lab while earning his doctorate. “That statistic further highlights the importance of considering a patient’s metabolic health alongside the biology of the tumor itself.”

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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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Four Weeks of Tomato-Soy Juice Lowered Inflammation in Adults with Obesity

Key Takeaways:

• In a four-week study, a tomato-soy juice rich in lycopene and soy isoflavones significantly reduced three blood markers of systemic inflammation in healthy adults with obesity, while a control tomato juice lacking those compounds did not.
  
• The researchers chose a low-carotenoid tomato juice as the comparison drink, rather than water, so they could isolate the effects of the lycopene and isoflavones rather than the effects of tomato juice in general.
  
• Building on these results and supporting animal data, the team has secured federal funding for a pilot clinical trial examining whether the same juice can ease inflammation in people living with pancreatitis.
  
  
  

A food-based approach to inflammation

Drinking a tomato-soy juice packed with plant compounds previously shown in animal studies to support health lowered pro-inflammatory proteins in healthy adults with obesity after four weeks, according to a new study. The researchers say the findings point to the juice’s potential as a functional food that could help rein in the persistent, unchecked inflammation that underpins a wide range of chronic conditions.

The juice was formulated to deliver high levels of two plant-based compounds, lycopene and soy isoflavones, both of which earlier research suggests have antioxidant and anti-inflammatory properties. Measured against a control tomato juice that lacked these compounds, the tomato-soy juice produced a significant drop in the blood levels of three proteins that serve as markers of systemic inflammation.

“The idea is, can we use food-based interventions to modulate inflammation?” said lead author Jessica Cooperstone, associate professor of horticulture and crop science at The Ohio State University. “And can we test this in a rigorous way so that we can really see this is affecting inflammation, versus just saying something is anti-inflammatory?”

The study was published recently in the journal Molecular Nutrition & Food Research.

What is in the juice

Lycopene is a carotenoid, the class of pigments responsible for the colours of tomatoes and various other vegetables. Soy isoflavones are flavonoids that mimic the action of the hormone oestrogen. Both are phytochemicals, naturally occurring compounds that help plants thrive.

Years ago, drawing on studies that linked diets rich in either tomato products or soy with a reduced risk of prostate cancer, Ohio State researchers developed the tomato-soy juice. It was made using tomatoes bred to contain a high concentration of lycopene – varieties also developed and grown at Ohio State – and then enriched with a soy isoflavone extract.

Subsequent research at the university connected a higher intake of the tomato-soy juice with reduced prostate-specific antigen levels in some men with prostate cancer. Studies conducted elsewhere have likewise suggested that tomatoes and soy, whether eaten separately or together, can influence inflammatory and metabolic pathways tied to obesity and other chronic illnesses.

“There’s been enough compelling evidence that compounds from tomatoes and soy might be modulating inflammation that we decided to test this in people,” Cooperstone said.

How the study was carried out

For the new study, 12 healthy adults with obesity drank two 6-ounce cans of the tomato-soy juice every day for four weeks. Following a washout period, the same participants then consumed the low-carotenoid control tomato juice for a further four weeks.

The choice of comparison drink was deliberate. Rather than pitting the juice against plain water, the team selected a tomato juice stripped of the key compounds so that any difference could be attributed to those compounds specifically.

“The hypothesis is that it’s the lycopene from the tomatoes and the isoflavones from the soy that’s inducing the effect, so we didn’t want to have a control that’s just water,” Cooperstone said.

What the blood tests showed

Before and after each four-week period, the researchers collected blood samples and tested them for cytokines, the pro-inflammatory proteins produced by the immune system. Only the tomato-soy juice produced significant reductions, and it did so in three cytokines: interleukin (IL)-5, IL-12p70 and granulocyte-macrophage colony-stimulating factor (GM-CSF). The juice was also associated with a downward trend in tumour necrosis factor alpha (TNF-a), although that particular change did not reach statistical significance.

Clues from the urine analysis

The team also examined participants’ urine before and after each trial period, looking for changes in metabolites. Metabolites are the molecular products of the biochemical reactions that break down nutrients to generate energy and carry out other essential functions in the body.

The analysis revealed that both the tomato-soy juice and the control tomato juice prompted some of the same shifts in metabolite profiles, indicating that certain tomato-driven effects occurred even in the absence of lycopene. Among the changes specifically induced by the tomato-soy juice, shifts in soy isoflavone metabolites stood out. The researchers note that, while more investigation is warranted, these changes offer further evidence that the food-based intervention is acting on human biology.

“This is probably a function of the fact that there’s more to our intervention agents than just these two compounds,” Cooperstone said. “Ultimately, we want to have a better understanding of how the foods that we eat are relating to our health. And when we really want to be sure, we need to test them in clinical trials. And that’s what we’re doing here.”

Next steps: a pancreatitis trial

On the strength of these results and additional data, Cooperstone and her colleagues have received funding from the National Institute of Diabetes and Digestive and Kidney Diseases for a pilot clinical trial. That trial will test whether consuming the same tomato-soy juice reduces inflammation in people living with pancreatitis.

The team has also gathered evidence from an animal model suggesting that the tomato-soy juice can lessen both inflammation and the severity of chronic pancreatitis. Those findings support the central prediction behind the new clinical trial, namely that the intervention could improve outcomes for people with the condition.

“Care for patients with pancreatitis is palliative, focused on controlling pain and GI symptoms. Our hypothesis is that the tomato-soy juice may serve as an intervention to decrease inflammation and hopefully increase patients’ quality of life,” Cooperstone said.

Funding and contributors

The work was supported by the U.S. Department of Agriculture, the National Institutes of Health, the Lisa and Dan Wampler Endowed Fellowship for Foods and Health Research, and the Foods for Health Initiative at Ohio State.

Co-authors include first author Maria Sholola, along with Jenna Miller, Emma Bilbrey, David Francis and Thomas Mace, all of Ohio State, and Janet Navotny of the USDA. Mace is the lead principal investigator on the pancreatitis trial. Cooperstone, Philip Hart and Kristen Roberts of Ohio State are also principal investigators on that trial.

Source: Eureka Alert!

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Year-Long Trial Finds Rapid Weight Loss Outperforms a Gradual Approach, Overturning a Long-Held Assumption

Key Takeaways:

• In a 52-week randomised trial, adults living with obesity who followed a rapid weight loss programme lost significantly more weight at one year than those on a gradual programme (14.4% versus 10.5% of total body weight), and the gap held throughout the study.
  
• Rapid weight loss was not associated with greater weight regain, directly contradicting the widespread belief that losing weight slowly is necessary to keep it off.
  
• A larger share of people in the rapid weight loss group reached clinically meaningful BMI and waist-to-height targets linked to a lower 10-year risk of obesity-related conditions.
  
  
  

A long-held belief comes under scrutiny

New research presented at the European Congress on Obesity (ECO 2026) in Istanbul, Turkey, indicates that rapid weight loss (RWL) is considerably more effective than gradual weight loss (GWL), both in the amount of weight people lose and in how well that loss is sustained at one year.

For years, conventional thinking has held that rapid weight loss is unhealthy and that shedding weight very quickly raises the chance of regaining it. Yet these concerns rest largely on observational data, historical assumptions, or small studies with methodological limitations. The scientific evidence directly supporting them is limited and inconsistent, and high-quality randomised controlled trial evidence remains relatively sparse.

The study was led by Dr Line Kristin Johnson of the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust in Tønsberg, Norway, together with colleagues. The centre is a collaborating centre with the European Association for the Study of Obesity (EASO-COM-Centre); EASO leads obesity advocacy and education across Europe and organises ECO.

Setting the treatment targets

A recent large, population-based cohort study concluded that, after weight loss, a body-mass index (BMI) of 27 kg/m² or below and a waist-to-height ratio (WHtR) of 0.53 or below may represent clinically meaningful treatment targets for lowering the 10-year risk of obesity-related complications, namely type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, and hip and knee osteoarthritis.

In this new study, the researchers set out to compare how effectively a rapid weight loss programme and a gradual weight loss programme helped people reach those targets.

How the trial was designed

The 52-week, investigator-initiated, randomised clinical trial was run as a collaboration between the Department of Endocrinology, Obesity and Nutrition at Vestfold Hospital Trust and Roede AS, one of Norway’s leading and most established providers of commercial weight loss programmes.

In total, 284 adults living with obesity (BMI of 30 or above), of whom 257 (90%) were women, were randomised on a one-to-one basis to one of two 16-week, food-based programmes. The rapid weight loss programme reduced energy intake in stages: under 1,000 kcal per day in weeks 1 to 8, under 1,300 kcal per day in weeks 9 to 12, and under 1,500 kcal per day in weeks 13 to 16. The gradual weight loss programme set intake at 800 to 1,000 kcal per day below each participant’s estimated total energy expenditure, with a mean self-reported intake in this group of roughly 1,400 kcal per day.

Estimated energy expenditure was calculated from each participant’s estimated resting energy expenditure and then adjusted according to whether they had low, medium, or high physical activity.

The food composition in both programmes followed current Norwegian dietary recommendations from the Norwegian Directorate of Health. Core advice included eating healthy foods such as vegetables, fruits, whole grains, low-fat dairy products, fish, eggs, lean meat, and other protein-rich foods, while limiting saturated fats and added sugars.

Maintaining the results

After the initial weight loss phase, participants in both groups moved into an identical 36-week weight-regain prevention programme.

Throughout the study, the interventions included weekly in-person group sessions from week 1 to week 16. After that, in-person group meetings took place every 14 days for the first three months, followed by monthly meetings or individual contact via webinars, video, or telephone for the remaining five months.

In these sessions, participants were advised to raise their daily energy intake by 100 to 300 kcal during the first month, until their weight stabilised. From then on, daily intake was adjusted as needed in response to any weight changes across the eight-month maintenance phase. Participants could decide for themselves whether to maintain their weight or aim for further loss, and the majority chose to keep losing weight after the initial 16-week period.

What the trial found

Of the 284 participants, 142 were randomised to the rapid weight loss programme and 142 to the gradual weight loss programme. At baseline, the rapid weight loss group had a mean age of 48.5 years, body weight of 102.4 kg, height of 169 cm, BMI of 35.8 kg/m², waist circumference of 112.5 cm, and WHtR of 0.67. The corresponding figures in the gradual weight loss group were 47.7 years, 103.0 kg, 168 cm, 36.5 kg/m², 112.8 cm, and 0.67.

The primary outcome was one-year percentage total body weight loss (%TBWL). The proportion of participants reaching a BMI of 27 kg/m² or below, or a WHtR of 0.53 or below, after one year were exploratory outcomes.

During the first 16 weeks, the rapid weight loss group lost significantly more weight than the gradual weight loss group, with a mean %TBWL of -12.9% compared with -8.1%, a between-group difference of -4.8%.

At one year, that significant difference was maintained: the mean %TBWL was -14.4% in the rapid weight loss group and -10.5% in the gradual weight loss group, a between-group difference of -3.9 percentage points.

The share of participants achieving a BMI of 27 kg/m² or below was significantly higher in the rapid weight loss group than in the gradual weight loss group at both 16 weeks (13.8% versus 0.8%) and one year (28.3% versus 9.7%). A higher proportion also reached a WHtR of 0.53 or below in the rapid weight loss group, both at 16 weeks (24.2% versus 8.9%) and at one year (33.0% versus 18.4%).

What the researchers say

The authors conclude, “Among adults with obesity, participation in a structured rapid weight loss program resulted in significantly greater weight loss at one year, and higher rates of achieving clinically meaningful BMI and WHtR targets compared with a gradual weight loss approach.

“These findings indicate that, when provided within a controlled and professionally supervised setting, rapid weight loss may represent a more effective method than gradual weight loss for reaching key body weight targets associated with reduced obesity-related health risks.”

Dr Johnson adds, “Our results clearly challenge the prevailing belief that slow and steady gradual weight loss is necessary to prevent weight regain and reduce obesity-related complications.

“By contrast, we show that rapid weight loss is not associated with weight regain, and, more importantly, that a larger proportion of participants undergoing rapid weight loss – compared with gradual weight loss – achieved clinically meaningful treatment targets for reducing the 10-year risk of type 2 diabetes, hypertension, atherosclerotic cardiovascular disease, and hip/knee osteoarthritis.

“These findings are particularly relevant given the urgent need for effective weight-loss and weight-maintenance strategies. As many individuals with obesity cannot access or afford medical or surgical treatments, our results support the potential of effective, commercially available weight-reduction programs to help reduce the growing burden on public health care systems.”

Why it matters

With obesity placing a rising strain on health systems, and with medical and surgical treatments out of reach for many, the trial points to professionally supervised commercial programmes as a potential route to meaningful, lasting results. Its central message reframes a long-standing assumption: under proper supervision, losing weight quickly did not undermine maintenance, and it helped more people reach the targets tied to lower long-term health risks.

CCH insights:

These are impressive results for a diet and lifestyle intervention, with both groups achieving greater than 10% total body weight loss over a period of a year. However, participants received fairly intensive support throughout the entire year of the trial. The important thing is what happens in the next 12 months, after the intervention has stopped – are they able to sustain behavioural changes and weight loss without the support from the programme?

Source: Medical Xpress

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AI-Powered Whole-Body Mapping Reveals Obesity’s Hidden Impact on Facial Nerves

Key Takeaways: 

• Researchers have developed an AI-driven whole-body imaging platform called MouseMapper that can analyse disease-related changes across an entire mouse body at cellular-level resolution.
  
• Using the system, scientists identified widespread inflammation and previously unknown damage to facial sensory nerves linked to obesity.
  
• Similar molecular patterns were also detected in human tissue, suggesting that obesity-related nerve changes observed in mice may also occur in people.
  
  
  

A new way to study disease across the entire body

Researchers from Helmholtz Munich, Ludwig Maximilians University Munich (LMU), and several collaborating institutions have developed a powerful artificial intelligence-based imaging system capable of mapping disease-related changes throughout an entire mouse body in extraordinary detail.

The new platform, known as MouseMapper, combines advanced whole-body imaging with foundation-model-based AI to examine how diseases affect organs, nerves, immune cells, and tissues simultaneously. Using the system, the research team uncovered widespread inflammation and previously unrecognised nerve damage associated with obesity.

The findings, published in Nature, also revealed similar molecular signatures in human tissue, suggesting that some obesity-related nerve damage mechanisms may occur in both mice and people.

Obesity is increasingly recognised as a complex disease that affects far more than body weight and metabolism. It can alter immune activity, disrupt nerve structures, and reshape tissues across the body, contributing to conditions including type 2 diabetes, cardiovascular disease, stroke, neuropathy, and cancer. However, despite these systemic effects, researchers have lacked technologies capable of studying disease-related changes throughout an intact body at high resolution.

To address this limitation, the research team led by Professor Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at LMU, created MouseMapper.

The AI framework uses deep learning algorithms based on foundation models to analyse enormous whole-body imaging datasets. The system can automatically identify and segment 31 different organs and tissue types while simultaneously mapping nerves and immune cells throughout the body.

This enables scientists to investigate how diseases affect multiple organ systems at the same time rather than analysing tissues individually.

“MouseMapper is built on a foundation model, which means it generalizes far beyond the data it was originally trained on,” says Ying Chen, co-first author of the study.

Transparent mice enable deep whole-body imaging

To generate the body-wide maps, the researchers first labelled nerves and immune cells in mice using fluorescent markers that glow under microscopic imaging.

The team then used specialised tissue-clearing techniques to render the mice transparent while preserving the fluorescent signals. This allowed scientists to visualise structures deep inside the body without physically cutting tissues into sections.

Researchers next employed advanced light-sheet microscopy to produce highly detailed three-dimensional images of entire mice. These scans generated extremely large datasets containing tens of millions of cellular structures distributed across multiple organs and tissues.

MouseMapper then processed the data automatically, identifying anatomical structures, nerve networks, and clusters of immune cells throughout the animals.

Unlike conventional approaches that require scientists to select specific tissues or regions for analysis beforehand, the system enabled the researchers to examine disease-related changes across the whole organism simultaneously.

This whole-body approach allowed the team to pinpoint where inflammation and tissue damage were occurring in organs including fat tissue, muscle, liver, and peripheral nerves.

Obesity found to alter facial sensory nerves

To investigate how obesity affects the body, the researchers fed mice a high-fat diet that induced obesity and metabolic disturbances similar to those observed in humans.

Using MouseMapper, the scientists identified widespread changes in both immune-cell organisation and nerve structures throughout the body.

One of the most unexpected findings involved the trigeminal nerve, a major facial nerve responsible for transmitting facial sensations and supporting certain motor functions.

The researchers discovered that obese mice showed a substantial reduction in nerve branches and sensory nerve endings within these facial nerves, suggesting impaired nerve function.

Behavioural testing supported this observation. Obese mice demonstrated reduced responsiveness to sensory stimulation compared with lean mice, indicating that the structural changes may have functional consequences.

Molecular changes detected in facial nerve tissue

The team then carried out a more detailed investigation of the trigeminal ganglion, the structure that contains the cell bodies of facial sensory neurons.

Using spatial proteomics analysis, the researchers identified molecular alterations associated with inflammation and nerve remodelling within the trigeminal ganglion.

Importantly, many of the same molecular signatures identified in mice were also found in trigeminal tissue samples from people living with obesity.

This suggests that the nerve-related changes observed in the animal models may also occur in humans.

“We revealed previously unknown structural and molecular changes in the trigeminal ganglion and its facial branches, and the same molecular signature was conserved in human tissue. This kind of finding simply cannot emerge from studying one organ at a time,” says Dr. Doris Kaltenecker, senior scientist at the Institute for Diabetes and Cancer (IDC) at Helmholtz Munich and first author of the study.

Potential applications beyond obesity

The researchers believe MouseMapper could become an important platform for studying diseases that affect multiple organ systems simultaneously.

Potential future applications include research into diabetes, cancer, neurodegenerative diseases, and autoimmune disorders.

Unlike traditional methods that focus on isolated tissues or organs, MouseMapper provides an integrated whole-body analysis system capable of identifying disease “hotspots” throughout an organism.

The research team has also made the whole-body datasets publicly available online, allowing scientists worldwide to explore obesity-related changes across tissues and organs.

“Our goal is to create a comprehensive framework for understanding how diseases affect the body as an interconnected system,” says Ali Ertürk.

“Our long-term vision is to build truly realistic digital twins of mice in health and disease: cell-level atlases that we can query, perturb and screen in silico computationally. That would let us pinpoint the earliest changes a disease causes, design interventions to prevent them, and accelerate the discovery of new treatments while reducing the number of physical experiments we need to run.”

Research funding and support

The study received support from multiple funding organisations and research initiatives, including the European Research Council, the German Research Foundation under Germany’s Excellence Strategy, the Munich Cluster for Systems Neurology (SyNergy), the German Federal Ministry of Education and Research, the Vascular Dementia Research Foundation, the Nomis Foundation, the Else-Kröner-Fresenius-Stiftung, the Edith-Haberland-Wagner Stiftung, the Helmut Horten Foundation, the EFSD and Novo Nordisk A/S Programme for Diabetes Research in Europe, and the China Scholarship Council.

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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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