Nutrition Gaps Raise Safety Concerns as Use of GLP-1 Weight Loss Drugs Accelerates
Key Takeaways:
- Many people prescribed GLP-1 weight loss medications receive little or no structured nutritional guidance, increasing the risk of preventable vitamin and mineral deficiencies and loss of muscle mass.
- New research highlights a lack of high-quality evidence on how diet quality, protein intake, and micronutrient intake are affected during treatment with drugs such as semaglutide and tirzepatide.
- Experts warn that without integrated nutritional care, the rapid expansion of GLP-1 drug use could undermine long-term health benefits despite effective weight loss.
Experts from University College London and the University of Cambridge are warning that many people prescribed newer weight loss medications may not be receiving sufficient nutritional guidance to support safe and sustainable weight loss. As a result, some individuals may face avoidable risks, including vitamin and mineral deficiencies and loss of lean body mass, particularly muscle.
The concerns arise from new research published in Obesity Reviews. Led by Dr Marie Spreckley of the University of Cambridge, the review identified limited high-quality evidence on how nutritional advice influences calorie intake, body composition, protein consumption, and patient experiences among people using these medications.
How GLP-1 weight loss drugs work
Drugs such as semaglutide and tirzepatide, sold under brand names including Ozempic, Wegovy, and Mounjaro, work by mimicking the action of glucagon-like peptide-1 (GLP-1). This hormone is released after eating and plays a role in regulating appetite and glucose metabolism. By enhancing feelings of fullness, reducing hunger, and dampening food cravings, these medications can substantially lower energy intake.
Studies suggest that calorie intake may fall by 16–39%, helping to explain why these drugs are highly effective for people living with obesity or overweight. However, the researchers note that there has been very little detailed study of how such reductions affect overall diet quality, protein intake, or micronutrient intake, including vitamins and minerals. Existing evidence indicates that lean body mass, including muscle tissue, can account for as much as 40% of total weight lost during treatment.
Experts warn of risks without nutrition support
Dr Adrian Brown, an NIHR Advanced Fellow at UCL’s Centre of Obesity Research and the study’s corresponding author, described how these medications alter eating behaviour.
“Obesity management medications work by suppressing appetite, increasing feelings of fullness, and altering eating behaviors, which often leads people to eat significantly less. This can be highly beneficial for individuals living with obesity, as it supports substantial weight loss and improves health outcomes.
“However, without appropriate nutritional guidance and support from healthcare professionals, there is a real risk that reduced food intake could compromise dietary quality, meaning people may not get enough protein, fiber, vitamins, and minerals essential for maintaining overall health.”
Without structured support, reduced intake may unintentionally lead to inadequate consumption of nutrients needed to preserve muscle mass, bone health, immune function, and overall physical resilience.
Public guidelines versus private use
Guidance from the National Institute for Health and Care Excellence recommends semaglutide for weight management only for people who meet strict eligibility criteria, such as a body mass index of at least 35.0 kg/m² alongside obesity-related comorbidities including type 2 diabetes or cardiovascular disease. When prescribed through the NHS, the medication is intended to be delivered as part of a comprehensive programme that includes dietary changes and increased physical activity.
In reality, most people currently using GLP-1 drugs in the UK obtain them outside the NHS. An estimated 1.5 million people are now using these medications, with around 95% accessing them through private providers. In these settings, ongoing nutritional advice and follow-up support are not always consistently offered.
Rising use outpaces nutrition guidance
Dr Spreckley, who works at the Medical Research Council Epidemiology Unit at the University of Cambridge, said nutritional care has not kept pace with the rapid uptake of these therapies.
“Use of GLP-1 receptor agonist therapies has increased rapidly in a very short period of time, but the nutritional support available to people using these medications has not kept pace. Many people receive little or no structured guidance on diet quality, protein intake, or micronutrient adequacy while experiencing marked appetite suppression.
“If nutritional care is not integrated alongside treatment, there’s a risk of replacing one set of health problems with another, through preventable nutritional deficiencies and largely avoidable loss of muscle mass. This represents a missed opportunity to support long-term health alongside weight loss.”
Low intakes of essential vitamins and minerals are associated with fatigue, impaired immune function, hair loss, and increased risk of osteoporosis. Loss of lean mass, most commonly muscle, can also raise the likelihood of weakness, injuries, and falls, particularly in older adults.
Limited research leaves major questions unanswered
The review identified only 12 studies that examined diet and nutritional outcomes alongside treatment with semaglutide or tirzepatide. These studies differed widely in how dietary advice was delivered and how nutritional outcomes were measured. Many lacked standardised methods and consistent reporting, making it difficult to draw firm conclusions about best practice.
Despite the rapid expansion of GLP-1 drug use, the researchers found little robust evidence to guide clinicians on how to support people nutritionally during treatment.
Lessons from bariatric nutrition care
Given the urgent need for practical guidance, the researchers suggest that interim lessons could be drawn from nutritional care used after bariatric surgery. Procedures such as gastric banding and gastric bypass lead to similar reductions in appetite and food intake.
Dr Cara Ruggiero, a co-author from the MRC Epidemiology Unit at the University of Cambridge, said established post-surgery principles could help address current gaps.
“While GLP-1 receptor agonists are increasingly used, there remains a clear gap in structured nutritional guidance. In the interim, we can draw on well-established post-bariatric nutrition principles. Our previous work highlights the importance of prioritizing nutrient-dense foods including high-quality protein intake, ideally distributed evenly across meals, to help preserve lean mass during periods of reduced appetite and rapid weight loss.”
The available evidence did not support recommending strict low-fat diets alongside GLP-1 therapies. However, some observational studies reported that people using these medications consumed relatively high amounts of total and saturated fat, suggesting a potential need for personalised guidance that aligns with national dietary recommendations.
Meal timing was rarely examined in clinical trials. Nevertheless, the researchers note that eating smaller meals more frequently may help manage side effects such as nausea and improve tolerability, particularly during the early stages of treatment.
Studying real-world experiences
The research team also emphasised the importance of incorporating the perspectives of people using GLP-1 medications into future studies. Understanding what types of information and support individuals find most helpful could improve real-world care and long-term outcomes.
To address this, the team has launched AMPLIFY – Amplifying Meaningful Perspectives and Lived experiences of Incretin therapy use From diverse communitY voices. The project aims to explore how people experience next-generation weight loss medications in everyday life.
“These medications are transforming obesity care, but we know very little about how they shape people’s daily lives, including changes in appetite, eating patterns, well-being, and quality of life,” Dr Spreckley said. “That’s what we’ll explore, working in particular with people from communities historically under-represented in obesity research, to help shape the future of obesity treatment.”
The research was funded by the National Institute for Health and Care Research, with additional support from the Medical Research Council and the NIHR UCLH Biomedical Research Centre.
CCH insights:
GLP-1 medications are licensed for the treatment of diabetes and obesity and they should be used alongside diet and lifestyle advice to improve cardiometabolic health. However, they are now commonly known as ‘weight loss drugs’, implying their primary aim is for people to lose weight. But this is kind of missing the point – the weight loss outcome is one of the mediating effects of the drugs which leads to improved health. However, if weight loss is not accompanied by a move to a healthy diet, which provides adequate levels of essential nutrients, then health outcomes will be compromised, as highlighted by this study.
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More Than One in Four Adults Worldwide May Be Eligible for GLP-1 Weight-Loss Medicines, Global Analysis Suggests
Key Takeaways:
- More than 27 percent of adults globally may be eligible for GLP-1 receptor agonists for weight management, based on pooled data from 99 countries.
- Eligibility is highest among women, older adults, and people living in low- and middle-income countries, raising significant questions around access and health equity.
- Researchers emphasise that medicines alone are not sufficient, and sustained investment in prevention and non-pharmacological obesity care remains essential.
A growing global obesity challenge
The worldwide prevalence of obesity has more than doubled over the past three decades, accompanied by sharp rises in weight-related conditions such as type 2 diabetes, cardiovascular disease, and several cancers. This escalating public health challenge places increasing strain on healthcare systems and national economies across the globe.
Against this backdrop, a new international study suggests that glucagon-like peptide-1 receptor agonists, commonly referred to as GLP-1 medications, could play a substantial role in addressing obesity and its related complications at scale. The analysis was co-led by investigators from Mass General Brigham and aimed to estimate how many adults worldwide might benefit from these medicines.
Large-scale global data analysis
Researchers from Mass General Brigham collaborated with colleagues at Washington University School of Medicine in St. Louis and Emory University’s Rollins School of Public Health to pool household health survey data from 99 countries, collected between 2008 and 2021.
The final dataset included 810,635 adults aged 25 to 64 years, selected based on the availability of key clinical measures, including:
- Body mass index
- Blood pressure
- Diabetes biomarkers
- Diagnostic history of hypertension and diabetes
Eligibility for GLP-1 treatment was defined using established clinical thresholds. Adults were considered eligible if they had:
- A BMI greater than 30, or
- A BMI greater than 27 in the presence of hypertension, diabetes, or both
One in four adults eligible worldwide
Using these criteria, the researchers found that 27 percent of adults globally would be eligible for GLP-1 medications for weight management. Notably, around four-fifths of eligible individuals lived in low- and middle-income countries, highlighting a potential mismatch between need and access.
Eligibility varied substantially by region:
- Europe and North America showed the highest rates at 42.8 percent
- The Pacific Islands followed closely at 41.0 percent
Differences were also observed across demographic groups:
- Women were more likely to be eligible than men, at 28.5 percent versus lower rates among men
- Older adults showed markedly higher eligibility at 38.3 percent, compared with 17.9 percent among younger adults
The findings were published as a research letter in The Lancet Diabetes & Endocrinology.
Rethinking obesity through biology
Commenting on the findings, co-senior author Jennifer Manne-Goehler, MD, ScD, a physician at Brigham and Women’s Hospital and Mass General Brigham, highlighted the paradigm shift represented by GLP-1 therapies.
“There has never been such a potentially transformational and scalable tool for obesity, type 2 diabetes, and other health-related complications of obesity.”
She also reflected on the historical framing of obesity as a personal failing rather than a biologically driven disease.
“For so many decades, we told everyone the problem was you – you need to move more and eat less, then you will not struggle with this problem. GLP-1 receptor agonists have allowed us to really understand that biology is much more powerful than that, and ‘eat less, move more’ is just an oversimplified way to think about things.”
Global interest meets practical constraints
The potential of GLP-1 medicines has already been recognised by the World Health Organization, which is actively exploring ways to make these treatments more widely available as standard therapies. However, translating this promise into real-world impact depends on understanding the scale of need and addressing significant barriers to access.
Corresponding author Sang Gune K. Yoo, MD, who conducted the work while a research fellow in cardiology at Washington University School of Medicine, noted that the findings were consistent with global obesity trends.
“Given the steadily increasing prevalence of obesity, it is not surprising that our analysis found that more than one quarter of adults around the world may be eligible for this medication.”
He cautioned, however, that important questions remain unanswered.
“This medication has the potential to help many individuals, although further research is needed to better understand its long-term safety and sustainability. Access remains a major challenge as these medications are difficult to obtain in many settings. Most importantly, we must continue to invest in and develop effective non-pharmacological strategies for the prevention and treatment of obesity, an area where substantial gaps remain.”
Equity at the centre of global implementation
The study also underscores profound equity considerations. Eligibility was disproportionately high among women and people living in regions with limited healthcare resources.
Manne-Goehler highlighted the urgency of addressing these disparities.
“These socioeconomic and gender eligibility percentiles are especially staggering. As of last year, type 2 diabetes was the top cause of death for women in South Africa. There are parts of the world where women can really benefit from these medicines, and it is our job to see through their implementation.”
Co-lead author Felix Teufel, MD, from Emory University’s Rollins School of Public Health, framed access to GLP-1 therapies as a broader ethical issue.
“Global access to GLP-1s is a question of health equity. The goal is to ensure large-scale access for people who would benefit most – not just those easiest to reach.”
Beyond medicines alone
While the findings point to a potentially transformative role for GLP-1 medications in global obesity care, the authors stress that pharmacological approaches cannot replace comprehensive prevention and treatment strategies. Addressing obesity at scale will continue to require sustained investment in public health, supportive environments, and evidence-based, non-pharmacological interventions alongside new medical therapies.
CCH insight:
This study reminds us of the scale of the obesity pandemic. There are more than 1 billion people estimated to be living with obesity, according to the World Health Organisation – most of whom could in theory benefit from GLP-1 medications. The priority should be to provide access for those who are in greatest need, rather than those who can afford to pay for them. The development of oral GLP-1s is a big step, as this will increase access and bring prices down, but there is a very long way to go.
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Wegovy Oral Obesity Treatment Launches in US Pharmacies Following FDA Approval
Key Takeaways:
- The oral form of Wegovy has launched in pharmacies, with the starting dose available now and higher doses expected shortly.
- Clinical trial data show weight loss outcomes comparable to the injectable version when taken as prescribed alongside dietary and activity changes.
- Pricing varies significantly depending on dose and insurance coverage, with list prices matching the injectable formulation.
Oral Wegovy becomes available nationwide
The oral form of Wegovy launched on Monday, with the starting dose now available in pharmacies across the country. Higher doses are expected to arrive by the end of the week, according to reports accompanying the launch.
The pill was approved by the Food and Drug Administration on 22 December for the treatment of obesity. It is also approved to reduce the risk of heart attack and stroke in people who are living with obesity or who are overweight.
Building on the success of the injectable formulation
The launch of the pill follows the blockbuster success of Novo Nordisk’s injectable Wegovy, which has been available since 2021. Demand for the injection was so high that it remained in short supply until February 2025.
Novo Nordisk has positioned the oral formulation as an alternative for people who prefer not to use injections, while maintaining similar clinical effectiveness.
Evidence from clinical trials
Clinical trial data suggest that the oral version of Wegovy delivers weight loss results comparable to the injectable form. In a study published in the New England Journal of Medicine, participants taking a 25 milligram Wegovy pill experienced an average weight reduction of 13.6% over 64 weeks. By comparison, participants receiving a placebo lost an average of 2.2% of their body weight.
Novo Nordisk estimates that people who remain on treatment, reduce their calorie intake and engage in regular physical activity could achieve an average weight reduction of 16.6%.
How the pill is taken and side effects
Unlike the injectable formulation, the Wegovy pill must be taken on an empty stomach. People are advised to wait at least 30 minutes before eating or drinking anything else to ensure the medicine is properly absorbed.
The most commonly reported side effects are similar to those seen with the injection and include nausea, diarrhoea and vomiting.
Pricing and insurance coverage
When Novo Nordisk announced a drug pricing agreement with the Trump administration in November, the company stated that it would offer the obesity pill for $149 per month to people not using health insurance. This price applies only to the starting dose purchased directly by consumers. Higher doses will be priced at $299 per month under the same arrangement.
The list price, which is used to determine insurance coverage, is set at $1,349 per month. This matches the list price of the injectable Wegovy.
Insurance coverage for obesity medications became more restrictive in 2025, according to an analysis from GoodRx, a website that helps people find discounts on prescription medicines. Novo Nordisk has said that people with insurance coverage may be able to access the Wegovy pill for as little as $25 per month.
How Wegovy compares with other oral GLP-1 medicines
Although the Wegovy pill is the first oral obesity treatment of its kind to receive FDA approval, Novo Nordisk already markets an oral GLP-1 medicine for Type 2 diabetes called Rybelsus. Rybelsus contains the same active ingredient, semaglutide, but is prescribed at different doses and is not approved for obesity.
Competition in the oral obesity drug market may soon increase. Eli Lilly, the manufacturer of the Zepbound injection, applied to the FDA in late 2025 for approval of its own obesity pill. The agency granted the company a priority review voucher, with a regulatory decision expected as early as this year.
CCH insight:
Hopefully oral Wegovy will be available in the UK soon, and at a more affordable cost than the injectable version. And this will hopefully enable increased access to the drug on the NHS. The current, very limited availability of GLP-1 therapy on the NHS is costing the UK tax-payer, because the cost of treating the complications and consequences of obesity is much greater than the cost of treating obesity – GLP-1s not only lead to weight loss, they reduce the risk of diabetes, heart disease, kidney disease and possibly many other conditions.
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Internalised Weight Stigma Places Heavy Emotional Burden on People Seeking Bariatric Care, Indian Study Finds
Key Takeaways:
- More than 71 percent of participants preparing for metabolic and bariatric surgery reported high levels of internalised weight bias, with many expressing self-blame, shame, and reduced self-worth.
- Younger individuals and those with a higher BMI reported stronger internalised stigma, which affected emotional well-being, social relationships, and readiness to seek treatment.
- Researchers and clinicians stress that obesity is a chronic disease, not a personal failing, and warn that stigma significantly harms mental health and delays access to appropriate care.
Introduction
A new study has highlighted the profound emotional and psychological toll experienced by people living with obesity who are preparing for metabolic and bariatric surgery. The research found that internalised weight bias is widespread among individuals seeking specialist care, with many reporting depressive symptoms, reduced self-esteem, and deep feelings of self-criticism linked to their weight.
The pilot study, titled The Burden from Within—An Indian Pilot Study on Weight Bias Internalisation, was published in Obesity Surgery, the international journal of the International Federation for the Surgery and Other Therapies for Obesity (IFSO).
Weight stigma beginning in childhood and persisting into adulthood
Lead author Dr Aparna Govil Bhasker, a Mumbai-based bariatric surgeon at the MetaHeal Laparoscopy and Bariatric Surgery Centre, told The Indian Express that stigmatising experiences often begin early in life. She explained that weight-related bullying is common during childhood and continues into adulthood for many people.
“People living with obesity are frequently judged as lazy or lacking willpower. Negative media portrayals, especially weight-based memes and stigmatising content, only deepen these harmful beliefs. Post-pandemic trends show that online negativity toward obesity has grown even stronger,” she said.
Study design and participant profile
To assess the emotional impact of obesity on people seeking surgical intervention, the research team evaluated 142 participants using the validated Weight Bias Internalization Scale (WBIS). Of the total cohort, 78.9 percent were women, and all participants had a body mass index of at least 27.5 kg/m².
Researchers examined total WBIS scores, associations with age, and correlations with BMI to understand how internalised stigma manifests in individuals preparing for metabolic and bariatric surgery.
High prevalence of internalised weight bias
The study revealed striking levels of internalised stigma:
- More than 71.1 percent of participants scored above the neutral benchmark on the WBIS, indicating widespread internalisation of negative weight-based beliefs.
- Around 74.6 percent reported feeling depressed about their weight.
- More than half felt less attractive because of their weight.
- More than one-third questioned their own competence.
The findings indicate that weight stigma does not simply come from external sources. Many participants had come to believe the negative stereotypes directed at them.
Self-judgement, self-hate, and social avoidance
The report found that more than half of the individuals surveyed expressed intense self-criticism, including feelings of self-hatred related to their weight. Many participants described weight as a defining measure of their personal worth.
Social relationships were also severely affected. Approximately 45.8 percent of participants questioned why anyone they considered attractive would want to date them. Half believed they did not deserve a fulfilling social life until they lost weight.
The data also showed that younger participants experienced stronger internalised bias, while those with higher BMI levels demonstrated deeper self-directed stigma.
“This shows that obesity status and internalisation of weight bias affect social interactions, connections, and relationships, which can have a long-lasting impact on the life course of an individual’s personal, emotional, occupational, and financial trajectory,” Dr Govil Bhasker said.
Obesity rising rapidly in India but not recognised as a disease
The researchers noted that obesity rates in India have nearly doubled since 2005. Data from the fifth National Family Health Survey (2019–21) show that 24 percent of women and 22.9 percent of men aged 15 to 49 years live with overweight or obesity.
Despite this rapid rise, obesity is not officially classified as a disease in India. Dr Govil Bhasker argued that the findings underline the deep societal stigma embedded in attitudes toward obesity.
“Patients often feel ashamed, guilty, and discouraged. They endure years of negative comments, judgment, and misinformation, and over time, these negative experiences become internalized. This affects their self-worth and mental health and can delay their decision to seek proper treatment. Obesity is a chronic disease, not a personal failure, and supporting patients emotionally is just as important as helping them medically,” she said. She added that targeted interventions are urgently needed.
Stigma’s broad impact on mental and physical health
Dr Vishakha Jain, Professor of Medicine at AIIMS BibiNagar and one of the study’s co-authors, emphasised that stigma infiltrates every aspect of daily life.
She explained that persistent stigma affects physical health, mental well-being, occupational performance, and social relationships. It can contribute to unhealthy eating patterns and biological stress responses, including increased inflammation.
“Together, these pressures create a cycle of self-blame and prejudice, often making individuals feel undeserving of care,” Dr Jain said.
Conclusion
The study provides compelling evidence that internalised weight stigma is highly prevalent among people preparing for bariatric care in India and that it carries profound psychological, social, and behavioural consequences. The authors urge greater recognition of obesity as a chronic disease and call for emotional as well as medical support for individuals affected.
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WHO Warns of Severe Global Shortages of GLP-1 Obesity Medicines as Demand Surges
Key Takeaways:
- Fewer than one in ten people worldwide who could benefit from GLP-1 medicines such as Wegovy and Mounjaro are currently able to access them, due to major limitations in production, affordability, and health system readiness.
- The World Health Organization has issued its first formal guidance on the clinical use of GLP-1 therapies, describing them as “a new chapter” in the treatment of obesity, but emphasising the need for equitable access and comprehensive lifestyle support.
- Without urgent action, global obesity prevalence is projected to double to two billion people by 2030, with associated economic costs reaching three trillion US dollars.
WHO Issues first guidance on GLP-1 medicines amid severe supply constraints
The World Health Organization has warned that fewer than one in ten people globally who could benefit from modern GLP-1 obesity medicines are currently able to obtain them, despite the scale of the obesity epidemic and the transformative clinical potential of drugs such as Wegovy and Mounjaro.
With more than one billion people worldwide now living with obesity, the WHO has called for far more widespread, affordable, and equitable access to GLP-1 therapies. Projections indicate that more than two billion people will be living with obesity by 2030 unless governments implement decisive action. The economic burden is expected to rise steeply, with global costs anticipated to reach three trillion US dollars by the same date.
Dr Tedros Adhanom Ghebreyesus, WHO Director-General, stressed that modern pharmacological treatments must be understood as part of a long-term care approach. He stated: “Our new guidance recognises that obesity is a chronic disease that can be treated with comprehensive and lifelong care. While medication alone will not solve this global health crisis, GLP-1 therapies can help millions overcome obesity and reduce its associated harms.”
The WHO has already added GLP-1 medicines to its essential medicines list for people who are overweight and living with diabetes, signalling that countries are advised to provide access to them. The organisation’s new guidance, described as a “special communication” aimed at clinicians, sets out for the first time its formal position on the value, limitations, and safe use of these drugs.
A new chapter in obesity treatment
The WHO notes that GLP-1 therapies represent “more than a scientific breakthrough”. They mark a decisive shift in how obesity is conceptualised, moving away from viewing it solely as a “lifestyle condition” and towards recognising it as a complex, preventable, and treatable chronic disease. The statement published in the Journal of the American Medical Association asserted: “GLP-1 therapies … have emerged as an important innovation in addressing the global obesity challenge. The advent of these medications represents a tipping point in the treatment of obesity, its complications and related co-morbidities.”
The WHO highlighted increasing evidence that GLP-1 therapies may also reduce the risk of several serious conditions, including heart attacks, strokes, type 2 diabetes, high blood pressure, elevated cholesterol, sleep apnoea, and kidney and arterial disease.
However, the organisation emphasised that these medicines must always be paired with holistic support. Individuals prescribed GLP-1s should receive advice on nutrition, physical activity, and behavioural counselling to maintain weight loss and improve long-term health outcomes. The WHO also reiterated that pregnant women should not use GLP-1 therapies.
Global access limited by production, affordability, and system capacity
Despite rising demand, global production capacity remains a major barrier. The WHO estimates that even under the most optimistic forecasts, manufacturers could produce enough GLP-1 medicines for only about 100 million people. This represents less than 10 per cent of the more than one billion who could benefit.
High prices, limited manufacturing capability, and supply chain constraints all significantly restrict access. The WHO has urged pharmaceutical companies to expand production rapidly and to reduce the prices of medications such as Mounjaro and Ozempic to prevent people in low-income countries from being excluded.
The guideline calls for measures such as voluntary licensing, through which patent-holding companies allow other manufacturers to produce low-cost generic versions. This pathway may soon become more viable as key patents expire. The patent on semaglutide, the active ingredient in Novo Nordisk’s Wegovy, is due to expire in several countries in 2026. Once this occurs, manufacturers in India, Canada, China, Brazil, Turkey, and other jurisdictions will be able to develop and sell more affordable versions.
The WHO also underscored three persistent barriers that must be addressed to achieve global access:
- Limited production capacity, availability, and affordability.
- Health system readiness to prescribe and monitor the medicines.
- Universal access to healthcare services.
Dr Tedros stressed the organisation’s “greatest concern is equitable access”.
Calls for national action on prevention and supportive environments
While pharmacotherapy can assist individuals living with obesity, the WHO stated that countries must continue to prioritise prevention and create healthier environments. This includes promoting physical activity, improving food systems, and ensuring that population-level interventions accompany advances in medical treatment.
How GLP-1 obesity medicines work
GLP-1 medicines work by mimicking a natural hormone that slows digestion, suppresses appetite, and increases feelings of fullness. This results in people eating less and typically losing weight within a few weeks of starting treatment.
In the United Kingdom, GLP-1 medicines are prescription-only and can only be supplied following clinical assessment by a healthcare professional. Some formulations are available through the NHS, although many are obtained privately. A black market for these medicines exists, and the WHO and UK regulators warn that people should avoid unregulated sources such as beauty salons or social media sellers.
Research suggests that people often regain much of the weight within a year after stopping GLP-1 therapy, as physiological hunger cues return. This further reinforces the need for comprehensive, long-term behavioural support.
Global obesity burden and associated risks
Obesity affects people in every country and was associated with 3.7 million deaths worldwide in 2024, according to the WHO. Being overweight or living with obesity increases the risk of numerous serious health conditions, including type 2 diabetes, cardiovascular disease, stroke, and several cancers. The WHO’s statement highlights the immense public health implications if access to effective interventions continues to lag far behind global need.
Expert commentary
The WHO statement was authored by senior clinicians Francesca Celletti, Luz De Regil, and Jeremy Farrar, the organisation’s Assistant Director for Health Promotion and Disease Prevention and Control. Dr Farrar formerly served as WHO Chief Scientist and Director of the Wellcome Trust in London.
Katherine Jenner, Executive Director of the United Kingdom’s Obesity Health Alliance, emphasised that medicines are only part of the solution. She stated: “Weight loss drugs have an important role to play, but they are not a silver bullet. In the United Kingdom right now, access is still limited, supply is fragile, and NHS use is tightly targeted. These powerful medicines can help individuals with chronic obesity, but they are not suitable for everyone and must be accompanied by comprehensive support to be used safely and effectively. Evidence shows that most people regain weight once they stop taking these drugs, and we cannot medicate two-thirds of the population indefinitely.”
CCH insight:
The limited supply of GLP-1 medicines globally is of course frustrating, but until new drugs come to market, and just liraglutide, semaglutide and tirzepatide available, this is likely to continue. All three of these drugs are polypeptides, delivered via injection ‘pens’ and must be refrigerated, so they are expensive and complicated to produce. However, new GLP-1 medications are in development which should improve access and reduce costs, such as orforglipron – a small molecule which is easier to produce and can be taken orally in pill form.
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Novo Nordisk’s Amycretin Emerges as a Strong Next-Generation Obesity and Diabetes Candidate in Early and Mid-Stage Trials
Key Takeaways:
- Early and mid-stage studies indicate that amycretin delivers substantial, dose-dependent weight loss in people who are overweight or have obesity, as well as in people with type 2 diabetes.
- Safety findings remain broadly consistent with GLP-1-based agents, with mainly mild to moderate gastrointestinal effects and no weight-loss plateau observed within study periods.
- Novo Nordisk’s new data signal a potentially important successor to semaglutide, strengthening the company’s obesity and diabetes pipeline as it faces patent expirations and competitive pressure from Eli Lilly.
Introduction
A new body of evidence published in The Lancet and released by Novo Nordisk suggests that amycretin, an investigational once-weekly therapy targeting multiple metabolic pathways, may offer clinically meaningful weight reduction and glycaemic improvements in adults who are overweight or have obesity, as well as in adults with type 2 diabetes. The findings come as Novo Nordisk aims to consolidate its leadership in the weight-loss market following concerns about semaglutide’s recent performance in Alzheimer’s trials and increasing competition from Eli Lilly.
Amycretin combines actions on the glucagon-like peptide 1 (GLP-1), amylin, and calcitonin receptors. This multi-pathway design is intended to amplify appetite suppression, slow gastric emptying, and improve metabolic control. Amylin’s role is particularly relevant because it complements GLP-1 signalling, and combining these effects may provide more durable weight management than existing single-pathway therapies.
Background
Obesity affects more than one billion people worldwide and increases the risk of conditions such as cardiovascular disease, type 2 diabetes, non-alcoholic fatty liver disease, and sleep apnoea. Although GLP-1 or GIP receptor agonists have transformed obesity care, many individuals still struggle to meet health goals or encounter diminishing returns over time. Enhancing these therapies with additional hormonal pathways, such as amylin, has been of growing scientific interest.
Amylin, a pancreatic hormone, naturally suppresses appetite, slows digestive transit, and moderates post-meal glucose spikes. When combined with GLP-1 activation, amylin may strengthen satiety signals and support deeper and more sustained weight reduction. Amycretin, a single peptide simultaneously targeting GLP-1, amylin, and calcitonin receptors, represents an effort to leverage these combined mechanisms.
While animal studies have shown potent metabolic effects, the safety, tolerability, and human efficacy of this multi-pathway approach had not been fully established, prompting the recently reported Phase 1b/2a trial and Novo Nordisk’s parallel mid-stage diabetes study.
Phase 1b/2a trial overview (adults who are overweight or have obesity)
Study design
Investigators conducted a five-part, randomised, placebo-controlled Phase 1b/2a trial at a single clinical site in San Antonio, Texas. Eligible adults were aged 18–55 years, had a baseline BMI between 27.0 and 39.9 kg/m², and had no major illnesses such as diabetes. Participants received subcutaneous amycretin or placebo once weekly.
The trial included:
- Part A: Single ascending doses (0.3 mg, 0.6 mg, 1.0 mg).
- Part B: Dose escalation to 60 mg over 36 weeks.
- Part C: Dose escalation to a 20 mg maintenance dose for the final 12 weeks of a 36-week period.
- Part D: Dose escalation to a 5 mg maintenance dose for the final 12 weeks of 28 weeks.
- Part E: Dose escalation to a 1.25 mg maintenance dose for the final 12 weeks of 20 weeks.
Endpoints and monitoring
The primary endpoint was the incidence of treatment-emergent adverse events. Secondary endpoints included:
- Percentage change in body weight
- Pharmacokinetic parameters
- Exploratory metabolic biomarkers (fasting glucose and HbA1c)
Participants had regular laboratory testing, ECG monitoring, and safety assessments. Analyses were adjusted for baseline weight and missing data.
Phase 1b/2a results
Participant characteristics
Between September 2023 and April 2024, the study enrolled 125 adults. A total of 101 received amycretin and 24 received placebo. Baseline BMIs ranged from 30.0 to 33.1 kg/m² across treatment groups, with an overall mean of 33.4 kg/m². Baseline weights ranged from 83.6 kg to 99.1 kg.
Tolerability and discontinuations
Thirty-eight participants receiving amycretin (37%) and four receiving placebo (17%) discontinued the study. Most discontinuations were not related to safety, and investigators noted that placebo discontinuations appeared consistent with a likely nocebo effect.
Treatment-emergent adverse events occurred in 92% of amycretin recipients and 100% of placebo recipients in Parts B–E. Gastrointestinal effects were most common and included:
- Nausea: 82%
- Vomiting: 53%
- Diarrhoea: 41%
These symptoms generally peaked during dose escalation and diminished afterwards. Dysaesthesia rates varied by cohort, ranging from 6% to 29%, and resolved in all but one participant.
One case of mild gallstone pancreatitis occurred during dose escalation in Part C (2.5 mg), later progressing to a serious recurrent episode that ultimately resolved.
No clinically meaningful ECG abnormalities were detected. A transient early rise in heart rate of about 10 bpm resolved without intervention. Antidrug antibodies appeared in 29% of Part B participants and 21% in Part C.
Weight-loss effects
Weight reduction was rapid, dose-dependent, and sustained. Mean percentage weight losses at end of treatment were:
- 60 mg (week 36): 24.3%
- 20 mg (week 36): 22.0%
- 5 mg (week 28): 16.2%
- 1.25 mg (week 20): 9.7%
Placebo groups had much smaller changes: −1.1% (Part B), +1.9% (Part C), +2.3% (Part D), and +2.0% (Part E).
Superiority to placebo emerged by week 4 and continued to widen without evidence of plateau during the maintenance phases. Repeated-measures models produced nearly identical weight-loss estimates.
Metabolic effects
Exploratory findings indicated modest improvements:
- Fasting glucose reductions up to 0.8 mmol/L
- HbA1c reductions of 0.6 percentage points in the highest-dose cohort
Lipid levels and seated blood pressure remained neutral.
Novo Nordisk’s mid-stage trial in type 2 diabetes
In parallel with the early-stage obesity trial, Novo Nordisk announced promising results from a mid-stage study evaluating amycretin in adults with type 2 diabetes who had inadequate glycaemic control with metformin, with or without an SGLT2 inhibitor. The trial included 448 participants and assessed both once-weekly subcutaneous and oral formulations.
Context and competitive landscape
The announcement came one day after Novo Nordisk reported disappointing Alzheimer’s trial results for semaglutide. With patent expirations approaching and rising competition from Eli Lilly’s amylin-based agent eloralintide, analysts are closely watching amycretin’s performance.
Amycretin is widely viewed as a potential “best-in-class” therapeutic candidate. It follows CagriSema, a combination approach which had raised strong expectations but ultimately delivered less weight loss than anticipated in prior studies.
Key findings
- Weight loss:
- Up to 14.5% weight reduction with once-weekly injections over 36 weeks
- Up to 10.1% weight reduction with the oral formulation
- Both routes showed no weight-loss plateau, suggesting the potential for further reduction with longer treatment durations.
- Up to 14.5% weight reduction with once-weekly injections over 36 weeks
- Glycaemic control:
- Statistically significant HbA1c reductions
- Up to 89.1% of participants achieved HbA1c below 7%
- Side-effects were mostly mild gastrointestinal symptoms.
- Statistically significant HbA1c reductions
Novo Nordisk stated it intends to begin late-stage clinical trials in 2026.
Analyst commentary
BMO Capital analyst Evan Seigerman noted that the data represent progress for Novo Nordisk:
“The data, though not enough to completely change the narrative for Novo, marks a step in the right direction for the company.”
Kepler Cheuvreux analyst David Evans commented on amycretin’s broader potential:
“The level of weight-loss seen bodes well not only for its potential in diabetes but also in obesity.”
Morningstar analyst Karen Andersen projected substantial commercial potential, estimating peak annual sales of $8 billion by 2034, split approximately evenly between diabetes and obesity indications, assuming a 2029 launch.
Conclusion
The combined early- and mid-stage data suggest that amycretin may represent a significant development in obesity and diabetes treatment. Its multi-pathway design has shown robust weight-loss effects across populations and the possibility of improved metabolic outcomes. While long-term safety and efficacy need confirmation in Phase 3 trials, amycretin appears positioned as one of Novo Nordisk’s most important next-generation candidates at a time of high strategic importance for the company.
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Weight Training Outperforms Running in Blood Sugar Control, Virginia Tech Mice Study Shows
Key Takeaways:
- Researchers at Virginia Tech found that resistance training was more effective than running in improving glucose tolerance and reducing insulin resistance in mice fed a high-fat diet.
- Both endurance and resistance exercise reduced body fat and improved blood sugar regulation, but resistance training yielded stronger metabolic benefits.
- The study suggests that strength training could play a particularly valuable role in preventing and managing Type 2 diabetes.
Weightlifting may offer unique metabolic benefits
Running is widely recognised for its cardiovascular and calorie-burning benefits, but new preclinical findings from the Fralin Biomedical Research Institute at Virginia Tech Carilion suggest that lifting weights may be even more effective for controlling blood sugar and reducing body fat.
Published on 30 October in the Journal of Sport and Health Science, the study compared the effects of endurance and resistance exercise in mice fed a high-fat diet, a common experimental model for obesity, hyperglycaemia, and Type 2 diabetes.
The team, led by Professor Zhen Yan, an exercise medicine researcher and director of the institute’s Centre for Exercise Medicine Research, found that while both running and weight training improved the body’s ability to clear excess glucose from the bloodstream, resistance training had a stronger impact on reducing both subcutaneous and visceral fat, improving glucose tolerance, and lowering insulin resistance.
“We all want to live a long, healthy life,” said Yan. “We all know the benefits of regular exercise. There is plenty of evidence in humans that both endurance exercise, such as running, and resistance exercise, such as weightlifting, are effective in promoting insulin sensitivity.”
Although both types of activity are known to improve metabolic function, the researchers noted that there had previously been no rigorous, controlled comparison between them.
Developing a model for ‘mouse weightlifting’
To address this gap, the Virginia Tech team created a first-of-its-kind preclinical model of resistance training in mice.
In their experiment, the mice lived in custom-built cages where food was available only through a hinged, weighted lid. To eat, the mice had to lift the lid while wearing a small shoulder collar, performing a movement similar to a human squat. The load was gradually increased over time, effectively replicating progressive strength training.
Meanwhile, the endurance group of mice was given unrestricted access to a running wheel, a standard model for voluntary aerobic exercise. Control groups included sedentary mice maintained on either a normal or high-fat diet.
Over an eight-week period, the researchers monitored changes in body weight, fat distribution, and body composition. They measured exercise capacity with treadmill tests, assessed cardiovascular and muscular performance, and evaluated blood sugar regulation. Muscle tissue samples were also analysed to study insulin signalling at the molecular level.
Using their novel resistance training model, the team could directly compare the metabolic outcomes of running and strength exercise under controlled conditions.
“Our data showed that both running and weightlifting reduce fat in the abdomen and under the skin and improve blood glucose maintenance with better insulin signalling in skeletal muscle,” Yan said. “Importantly, weightlifting outperforms running in these health benefits.”
Implications for obesity and diabetes prevention
Obesity and Type 2 diabetes remain among the most pressing public health challenges, driven largely by high-fat diets and sedentary lifestyles. The new study supports existing clinical evidence showing that endurance, resistance, and high-intensity interval training all contribute to better long-term blood sugar control, reduced body mass index, lower blood pressure, and improved overall well-being.
However, this Virginia Tech study fills a critical gap by directly comparing the two types of exercise in a controlled model of diet-induced obesity. The findings may have important implications for exercise recommendations and diabetes prevention strategies.
“The findings also bring good news for people who, for any number of reasons, cannot engage in endurance-type exercise,” Yan explained. “Weight training has equal, if not better, anti-diabetes benefits.”
Exploring new mechanisms and future therapies
The researchers also observed molecular changes in skeletal muscle that may help explain the enhanced benefits of resistance training. These shifts in insulin signalling pathways could, according to the team, inform the development of new drug therapies for managing Type 2 diabetes.
Interestingly, the improvements seen with resistance training were not directly linked to increased muscle mass or superior exercise performance, suggesting that unique metabolic mechanisms may be at work.
Yan emphasised that although pharmacological interventions such as GLP-1 receptor agonists are valuable tools in diabetes management and weight loss, they cannot replace the broad, systemic benefits of physical activity.
“The take-home message is that you should do both endurance and resistance exercise, if possible, to get the most health benefit,” he said.
The study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health and by the Red Gates Foundation, with collaborators from the University of Virginia contributing to the work.
CCH insights
This is an interesting study, but it is important to note it was conducted in mice, not humans. Having said that, perhaps the most reassuring thing about these results is that both types of exercise provided metabolic health benefits. The critical thing about physical activity is that any amount and type is better than doing none, and while a combination of endurance and resistance is probably best, if you can only manage one type or the other, it will have a positive impact.
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Thousands in Scotland’s Poorest Areas to Receive Free Weight-Loss Jabs in Landmark Obesity Study
Key Takeaways:
- Up to 5,000 adults living with obesity in Scotland’s most deprived areas will receive free weight-loss injections through the new Scotland CardioMetabolic Impact Study (SCoMIS).
- The multi-million-pound research, led by the University of Glasgow, aims to test the real-world delivery and impact of incretin-based therapies in NHS care.
- The study seeks to reduce health inequalities, improve quality of life, and lessen the long-term burden of obesity on individuals and the NHS.
Landmark initiative targets obesity in Scotland’s most deprived communities
Thousands of people from some of Scotland’s most economically deprived areas will soon be offered free weight-loss injections as part of a major UK government-funded study. The initiative, known as the Scotland CardioMetabolic Impact Study (SCoMIS), will recruit between 3,000 and 5,000 participants living with obesity to test how new weight-loss medicines can be delivered effectively and fairly in everyday NHS care.
The research is being led by the University of Glasgow and is backed by an initial £650,000 in funding from the UK government. If successful, it could pave the way for a wider rollout of the medicines across the country, offering a model for addressing both obesity and health inequality.
How the jabs work
The injections mimic or enhance the effects of naturally occurring hormones called incretins, which help control blood sugar levels. These hormones act on areas of the brain that regulate hunger and appetite and can also slow down how quickly the stomach empties. Together, these effects may support people living with obesity to better manage their eating habits and achieve sustained weight loss.
A national effort to reduce health inequality
Dr Zubir Ahmed, UK Health Innovation Minister, said:
“As a practising NHS surgeon and Glasgow MP, I know firsthand the impact of the obesity crisis that plagues Scotland – and the litany of health problems it leads to. More than 1 in 3 adults in Scotland’s most deprived areas are living with obesity. The UK government is committed to tackling inequality wherever it finds it in our country. It’s why this landmark UK government investment is targeting help where it’s needed most in Scotland and meeting people where they are and backing helping the NHS services they trust to treat them.”
Obesity is one of the leading contributors to long-term illness, including heart disease, type 2 diabetes, and several cancers. By addressing obesity through targeted intervention, the UK government hopes to help millions live longer, healthier lives while reducing the strain on the NHS and saving billions in healthcare costs each year.
Study objectives
The SCoMIS trial will evaluate several key areas of impact:
- Delivery: How weight-loss medicines can be integrated into everyday NHS care, especially within community and primary care settings.
- Outcomes: The degree of weight loss achieved and improvements in quality of life, particularly among people from disadvantaged areas.
- Health impact: The effects on obesity-related conditions, NHS service use, and healthcare expenditure.
- Social benefits: Whether improved health through weight loss can help individuals remain in work, reduce sick leave, and participate more fully in society.
Leading experts and national collaboration
Professor Jason Gill, Professor of Cardiometabolic Health at the University of Glasgow and the lead investigator, said:
“While tackling obesity requires multifactorial public health action, incretin therapies add a powerful new tool to the national obesity strategy. The burden of obesity is greatest in the most deprived segments of society and the status quo risks widening health inequalities. SCoMIS aims to be a landmark real-world study evaluating a new model of obesity care, providing incretin treatment via primary and community care to Scottish adults living with obesity, with a focus on those in the most economically deprived communities.”
The project is being developed in collaboration with the Universities of Dundee and Edinburgh, industry partners Novo Nordisk and IQVIA, and clinical leaders across Scotland. The consortium will also explore how AI-driven digital technologies can improve patient access, engagement, and data collection throughout the study.
Supporting innovation and evidence-based care
Jenni Minto, Scottish Minister for Public Health, highlighted Scotland’s leadership in advancing obesity research:
“This study places patients and communities at the heart of cutting-edge research into weight-loss medicines, ensuring we build the evidence needed to deliver the greatest benefit to those who need it most.”
UK Science Minister Lord Vallance also praised Scotland’s role in global medical innovation:
“Scotland has always been at the forefront of medical innovation and public health, and this initiative is further proof of the world-class expertise that can be found here. By learning how these weight-loss medicines work, and how we can support them to reach our most deprived areas, we can slash health inequalities in Scotland and the rest of the UK so that our obesity strategy delivers a real, lasting change.”
Looking ahead
Set to launch next year, the SCoMIS study represents one of the most ambitious real-world obesity trials in the UK to date. Its outcomes are expected to shape future national strategies on obesity care, providing a template for equitable access to advanced weight-loss treatments and supporting a healthier, more inclusive society.
CCH insights
This study is very much welcomed, although arguably long overdue. Obesity and associated diseases, most notably type 2 diabetes and cardiovascular disease, are most prevalent in communities with high levels of deprivation, and are a huge cost to the NHS. People in these communities living with obesity should be prioritised in terms for GLP-1 therapy, as this should help to drive down health inequalities and provide massive future financial savings for the health service.
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GLP-1 Weight Loss Drugs Linked to First National Decline in Obesity Rates, Survey Finds
Key Takeaways:
- The U.S. adult obesity rate has dropped from 39.9% to 37% over three years, coinciding with a rapid rise in GLP-1 medication use.
- Over 12% of adults now report taking injectable obesity drugs such as semaglutide or tirzepatide, more than double the proportion from early 2024.
- Experts warn that limited insurance coverage may soon hinder access, potentially reversing progress.
New survey suggests decline in U.S. obesity rates
The proportion of adults living with obesity in the United States has declined for the first time in years, according to a new Gallup National Health and Well-Being Index survey. The findings suggest that the surge in the use of injectable obesity drugs may be driving this shift.
The survey reported that 37% of U.S. adults are currently living with obesity, compared with a peak of 39.9% three years ago. Researchers attribute much of this reduction to the growing uptake of GLP-1 receptor agonists, a class of highly effective weight loss drugs that include semaglutide and tirzepatide.
Use of GLP-1 medications has more than doubled
The number of people using GLP-1-based treatments such as Ozempic and Wegovy (semaglutide), or Zepbound and Mounjaro (tirzepatide), has more than doubled over the past 18 months. According to Gallup, 12.4% of respondents reported using these drugs, up from 5.8% in February 2024, when the organisation first began tracking their use.
GLP-1 receptor agonists, which mimic a naturally occurring hormone that regulates appetite and blood sugar, were first approved for obesity treatment in 2021. Their mechanism of action involves acting on the brain and gut hormones to suppress hunger and slow digestion, helping individuals sustain weight loss.
A watershed in obesity treatment
Experts consider the introduction of GLP-1 receptor agonists to be a landmark in obesity treatment, following decades of limited progress through diet, exercise, and public health campaigns.
Gallup described the new generation of GLP-1 drugs as a “watershed in Americans’ long struggle to address obesity and related diseases.” Despite these advances, the survey also found that diabetes rates have reached a record high: 13.8% of adults reported having been diagnosed by a doctor or nurse. This highlights the scale of ongoing metabolic health challenges even as weight loss interventions improve.
Impact seen most among middle-aged adults and women
The data indicate that the reduction in obesity rates has been most notable among adults aged 40 to 64, a demographic more likely to use GLP-1 medications. Among those aged 50 to 64, obesity prevalence fell by 5.0 percentage points, reaching 42.8%.
The survey also noted differences by sex: women were more likely than men to use these medications and tended to report greater weight loss benefits. This aligns with previous clinical research showing that women are often more proactive in seeking medical support for weight management.
Access and affordability remain key challenges
Despite their effectiveness, access to GLP-1 drugs remains uneven and may worsen in the coming year. Dr Fatima Cody Stanford, an obesity specialist at Harvard University, cautioned that while the correlation between increased access and reduced obesity rates is promising, it may not be sustainable if coverage declines.
“I would say this correlation happened for those that had great coverage, but it’s going to be pulled back,” she said.
Dr Stanford explained that several private insurers – including those covering most of her patients – are planning to stop covering GLP-1 medications as of next year. Without insurance, the cost of injections typically reaches around $500 per month out of pocket, she noted.
Although pharmaceutical companies are developing oral versions that may eventually reduce costs, Dr Stanford warned that these treatments will likely remain unaffordable for many in the short term.
“While drugmakers are working to bring potentially less-expensive pill versions to market, it likely still will put the treatments out of reach for many,” she said.
Slow but significant progress
While the findings do not confirm causation, they offer one of the first indications that the widespread use of GLP-1 receptor agonists could be contributing to measurable declines in obesity prevalence. Public health experts stress, however, that long-term trends will depend heavily on sustained access, equitable prescribing, and broader changes in lifestyle and preventive care.
For now, the data mark a tentative but meaningful turning point in the decades-long fight against obesity in the United States – a shift that could influence obesity strategies worldwide if sustained.
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Exercise Shown to Reduce Artery Hardening After Weight Loss in Adults With Obesity
Key Takeaways:
- Regular exercise after weight loss significantly reduces inflammation and improves blood vessel health in adults living with obesity.
- The GLP-1 receptor agonist liraglutide helped participants maintain weight but did not show the same protective effects against artery hardening.
- Researchers emphasise exercise as an essential factor for maintaining cardiovascular health after weight reduction.
Exercise and heart health after weight loss
Maintaining weight loss through regular exercise, rather than relying solely on the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, appears to protect against atherosclerosis in adults living with obesity, according to new research from the University of Copenhagen. Atherosclerosis—hardening and narrowing of the arteries due to inflammation and fat deposits—is a major underlying cause of cardiovascular disease (CVD).
The findings were presented at the Annual Meeting of the European Association for the Study of Diabetes (EASD) 2025 in Vienna (15–19 September).
“Our findings reveal that regular exercise is crucial to helping people living with obesity get the full cardiovascular benefits after a substantial weight loss,” said Dr Rasmus Sandsdal, lead author of the study from the University of Copenhagen, Denmark.
Understanding the risk
Cardiovascular disease remains the leading cause of death globally. It often begins with atherosclerosis, in which chronic inflammation and lipid accumulation cause the arteries to stiffen and narrow. If left unchecked, these plaques can rupture and trigger life-threatening events such as heart attacks and strokes.
Obesity contributes to chronic low-grade inflammation and endothelial dysfunction—a condition in which blood vessels lose their ability to contract and relax properly—both of which accelerate atherosclerosis.
While both exercise and GLP-1RAs are known to lower cardiovascular event risk in people with obesity, their specific effects on the development of atherosclerosis during weight loss maintenance have remained unclear—until now.
The study design
The Danish research team conducted a randomised placebo-controlled trial involving 215 adults aged 18–65 years (63% female) living with obesity (BMI 32–43 kg/m²) but without diabetes or other serious chronic conditions.
All participants began an eight-week low-calorie diet (800 kcal per day) using the Cambridge Weight Plan. Of these, 195 participants who achieved at least a 5% reduction in body weight (average loss of 12% or 13.1 kg) entered a one-year maintenance phase. They were randomly assigned to one of four groups:
- Exercise (150 minutes/week of moderate-to-vigorous activity) plus placebo
- Liraglutide treatment (3.0 mg per day)
- Exercise combined with liraglutide
- Placebo only
Researchers measured several key biomarkers at three points—before dieting, at the start of weight maintenance, and after one year. These included inflammatory markers (interleukin-6 [IL-6] and interferon-γ [IFN-γ]), endothelial function markers (intercellular adhesion molecule [ICAM-1], vascular adhesion molecule [VCAM-1], and tissue plasminogen activator [tPA]), and carotid artery intima-media thickness [cIMT], an indicator of arterial wall health measured by ultrasound.
Exercise reduced inflammation and improved arterial health
After one year, participants in both the exercise and liraglutide groups successfully maintained their weight loss. However, significant differences emerged in their cardiovascular health profiles.
Those who exercised—whether or not they also received liraglutide—had notably lower levels of inflammatory biomarkers compared with non-exercising participants. On average, IL-6 levels were 21% lower, and IFN-γ levels were 27% lower.
Exercise also had a favourable effect on endothelial function, reflected in a 6% reduction in VCAM-1, 8% reduction in ICAM-1, and 12% reduction in tPA compared to those who did not exercise. Moreover, carotid artery thickness decreased by an average of 0.024 mm, indicating reduced arterial hardening.
In contrast, treatment with liraglutide alone did not yield any measurable improvements in inflammatory or endothelial biomarkers, nor did it affect carotid artery thickness.
“Regular exercise seems to confer a protective effect against the development of atherosclerosis in people trying to maintain weight loss,” said Dr Sandsdal. “Since both exercise and GLP-1RA treatment were successful at keeping weight off, it seems that exercise plays an important role in mitigating cardiovascular risk factors in a weight-independent manner.”
Implications for long-term health
Exercise offers multiple benefits beyond weight control, including improvements in body composition, cardiorespiratory fitness, and metabolic health. Together, these contribute to better long-term cardiovascular outcomes.
“The most important message from our findings is that, for those trying to maintain weight loss, exercise is crucial in improving long-term health,” said Professor Signe Sørensen Torekov, corresponding author from the University of Copenhagen. “Given the substantial societal and economic costs of obesity-related cardiovascular disease, these findings underscore regular exercise as a critical component of weight management and heart health.”
Study limitations and future research
The authors acknowledged several limitations. The study’s sample size was relatively small, and adherence to structured exercise in real-world conditions may be lower than in a supervised trial setting.
Future studies, they suggested, should explore longer-term interventions and evaluate newer GLP-1 receptor agonists—potentially more potent than liraglutide—in combination with consistent exercise to assess whether similar or enhanced cardiovascular benefits can be achieved.
CCH insight:
We have long known that exercise is important for cardiovascular health, so the results of this study should not be a surprise – exercise provides cardiovascular benefits whether or not you are taking a GLP-1 medication. It is also important to remember that GLP-1 receptor agonists are meant to be taken as an adjunct to a healthy diet and lifestyle, including exercise. This is not just about weight management, but also about maximising health benefits and minimising the risk of developing diseases associated with obesity – such as cardiovascular disease.
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Use of GLP-1 Drugs Soars Among People Undergoing Bariatric Surgery, Study Finds
Key Takeaways:
- The use of GLP-1 receptor agonists such as semaglutide and tirzepatide among bariatric surgery patients increased sixteenfold between 2020 and 2024.
- Both people with and without Type 2 diabetes are increasingly using these drugs, showing a shift toward combination approaches in obesity management.
- Researchers emphasise the importance of multidisciplinary care and call for evidence-based guidelines to optimise the use of GLP-1 drugs alongside surgery.
A rapid evolution in obesity care
New research has revealed a dramatic increase in the use of weight loss medications among people undergoing metabolic and bariatric surgery, signalling a major shift in the treatment of obesity and Type 2 diabetes.
The study will be presented at the American College of Surgeons (ACS) Clinical Congress 2025, held in Chicago from 4–7 October.
“There is no one-size-fits-all approach to treating obesity, metabolic syndrome, or diabetes and its related conditions,” said Dr Patrick J. Sweigert, senior author of the study and bariatric and foregut surgeon at The Ohio State University Wexner Medical Center in Columbus, Ohio. “We are entering a new world of multidisciplinary care pathways and a new frontier of weight management that is important for patients and surgeons to think about.”
About the study
The research team conducted a large cross-sectional study examining the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) – specifically semaglutide (marketed as Wegovy and Ozempic) and tirzepatide (marketed as Zepbound and Mounjaro) – among people undergoing metabolic and bariatric surgery.
Using data from the Epic Cosmos database, which aggregates over 300 million patient records from healthcare institutions across the United States, Dr Sweigert and colleagues analysed nearly 365,000 individuals who underwent primary metabolic and bariatric surgery between 2018 and 2024.
The study assessed prescription patterns for semaglutide and tirzepatide, two of the most widely prescribed GLP-1RAs, to understand how their use has evolved before surgery.
Key findings
Preliminary findings showed a striking rise in GLP-1 prescriptions in the year preceding surgery – from 1.8% in early 2020 to 29.4% by the end of 2024, representing a sixteenfold increase.
Importantly, the surge was seen among people both with and without Type 2 diabetes, demonstrating the expanding role of GLP-1 drugs in obesity treatment beyond diabetes management.
Among those without Type 2 diabetes, use of GLP-1 drugs before surgery increased elevenfold – from 2.1% in early 2022 to 23.2% by late 2024. For those with Type 2 diabetes, preoperative use quadrupled – from 11.3% to 45.2% over the same period.
The median age of participants was 43 years, with a median preoperative body mass index (BMI) of 46. Women accounted for 80% of the cohort, and 33% had a diagnosis of Type 2 diabetes.
Changing perceptions and treatment pathways
Lead author Dr Stefanie C. Rohde, a general surgery resident at The Ohio State University Wexner Medical Center, explained that the findings represent an evolution in how people view their treatment options for obesity.
“While patients previously believed they had to choose between GLP-1 receptor agonists and surgery, we are now seeing that people are using both,” said Dr Rohde. “We know that patients can use GLP-1s after bariatric surgery to amplify their weight loss. But all of this is still very new in terms of how to manage patients effectively.”
She added that real-world data such as that provided by the Epic Cosmos network could play a critical role in establishing evidence-based clinical guidelines for how and when to integrate GLP-1 therapies – whether before surgery, in combination with it, or during postoperative follow-up.
Limitations and next steps
The researchers acknowledged several limitations. As with many analyses of large health databases, there may be inaccuracies in medical record data. The study was also unable to confirm whether individuals filled or took their prescribed medications, which could affect the reliability of prescription data.
Despite these caveats, the authors believe the study offers valuable insights into emerging trends in combined pharmacological and surgical approaches to obesity care.
Study co-author Mahmoud Abdel-Rasoul, MS, MPH, contributed to the data analysis and interpretation.
Looking ahead
The rapid rise in GLP-1 use among bariatric surgery candidates reflects a broader transformation in obesity treatment – one increasingly characterised by personalised, multidisciplinary, and data-informed care.
As Dr Sweigert noted, “We are entering a new world of multidisciplinary care pathways.” The challenge now lies in defining the most effective, safe, and sustainable ways to integrate these groundbreaking medications into established surgical treatment frameworks.
CCH insight:
These findings from the ACS, showing GLP-1 drug use prior to bariatric surgery, follow on from another study showing that many patients use GLP-1 drugs after surgery, in order to prevent weight regain. This will hopefully help to shift the thinking around obesity treatment. There is still a common perception that patients with obesity have the option of medication or bariatric surgery, and that it is a ‘one-and-done’ treatment. However, we know that obesity is a complex, chronic, relapsing disease which requires a long-term, multi-disciplinary approach. So we need medications, we need surgery and we need behavioural support and other interventions, used together in various combinations, at different times, to provide the life-long care that obesity patients require.
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Oral GLP-1 Therapy Orforglipron Demonstrates Significant Weight Loss in Landmark Trial
Key Takeaways:
- The ATTAIN-1 phase III trial found that the oral GLP-1 drug orforglipron led to clinically meaningful weight loss and metabolic improvements in people living with obesity or overweight.
- Average weight loss reached 12.4% with the highest dose, alongside significant improvements in waist circumference, blood pressure, and lipid profiles.
- Orforglipron may provide a more accessible alternative for individuals reluctant to use injections or living in areas with limited cold-storage infrastructure.
A new oral alternative to injectable GLP-1 therapies
An investigational oral GLP-1 drug, orforglipron, has been shown to promote substantial weight loss and improve cardiovascular and metabolic health markers in a large, international phase III clinical trial. The ATTAIN-1 study, published on 17 September in The New England Journal of Medicine, was led by researchers from Weill Cornell Medicine, McMaster University, York University, and collaborating institutions.
The study enrolled 3,127 participants with obesity or overweight who had obesity-related complications such as hypertension. None of the participants had diabetes. Participants were randomised to receive a placebo or one of three daily oral doses of orforglipron – 6 mg, 12 mg, or 36 mg – alongside guidance on maintaining a healthy diet and regular physical activity.
Meaningful weight loss across all doses
Over 72 weeks, individuals treated with orforglipron experienced dose-dependent weight loss:
- 7.8% reduction in body weight with the 6 mg dose
- 9.3% reduction with the 12 mg dose
- 12.4% reduction with the 36 mg dose
By comparison, participants in the placebo group lost an average of just 2.1% of their initial body weight.
Adverse events were consistent with those observed for other GLP-1 receptor agonists, mainly mild to moderate gastrointestinal effects including nausea, vomiting, and diarrhoea.
Clinical and public health implications
“The findings suggest that orforglipron could offer an important new option for people with obesity, especially those reluctant to use injections or who live in places where cold storage for injectable medications is limited,” said Dr Louis Aronne, Director of the Comprehensive Weight Control Center and Sanford I. Weill Professor of Metabolic Research at Weill Cornell Medicine, who served as a lead investigator for the ATTAIN-1 trial.
“ATTAIN-1 represents another milestone in developing effective treatments for obesity. In addition, the distribution and storage of a small molecule is less expensive, and scalability is simpler. Given the worldwide demand, these are important factors in making treatment available to those in need,” Dr Aronne added.
Dr Aronne is also an internist specialising in diabetes and obesity at NewYork-Presbyterian/Weill Cornell Medical Center.
Improvements beyond weight loss
Although the weight reduction achieved with orforglipron was slightly lower than that typically seen with injectable GLP-1 therapies such as semaglutide or tirzepatide, the study reported robust cardiometabolic benefits. Participants on orforglipron demonstrated greater reductions in:
- Waist circumference
- Systolic blood pressure
- Non-HDL cholesterol and triglyceride levels
- Glycated haemoglobin (HbA1c)
These improvements underline the drug’s potential to reduce the risk of major obesity-related complications, including cardiovascular disease and type 2 diabetes.
Why oral GLP-1 drugs could be game-changing
Injectable GLP-1 drugs, which are peptide-based therapies, have already transformed obesity and type 2 diabetes management worldwide. When taken long-term, they can help people lose more than 15% of their body weight and substantially lower the risk of heart attack, stroke, kidney disease, and sleep apnoea.
However, injectable GLP-1 medications require cold storage and are vulnerable to breakdown by stomach enzymes if taken orally. Orforglipron is different – it is a “small-molecule” drug designed to be taken as a pill, potentially lowering costs and simplifying global distribution.
Study scope and sponsorship
The ATTAIN-1 trial was sponsored by Eli Lilly and Company, which manufactures orforglipron as well as the injectable GLP-1 drug tirzepatide (marketed as Mounjaro for type 2 diabetes and Zepbound for chronic weight management). The trial was conducted across 137 sites in nine countries, including the United States, Canada, Japan, Brazil, Spain, and Saudi Arabia.
Disclosure: Dr Louis Aronne serves as a paid consultant and advisory board member for Eli Lilly and Company.
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