Study Suggests GLP-1 Medications May Reduce Frailty Progression in Older Adults
Key Takeaways:
- Older adults with type 2 diabetes who begin SGLT-2 inhibitors or GLP-1 receptor agonists show slower frailty progression over one year compared with those starting other diabetes therapies.
- The analysis, based on a large national Medicare dataset, suggests these medications may offer benefits beyond glycaemic and cardiovascular control, potentially supporting strength, mobility, and functional independence.
- The protective effect was not fully explained by fewer cardiovascular or safety events, indicating a possible direct influence of these drug classes on frailty itself.
Emerging evidence that newer diabetes drugs may protect against frailty
A new study has found that older adults living with type 2 diabetes who initiate treatment with sodium–glucose cotransporter-2 (SGLT-2) inhibitors or glucagon-like peptide-1 (GLP-1) receptor agonists experience significantly slower progression of frailty over a 12-month period compared with those starting alternative diabetes medications. The findings point to a potential added advantage of these therapies in helping older adults maintain physical resilience, strength, and independence, complementing their established effects on blood glucose regulation and cardiovascular risk reduction.
Study overview and methods
The research, published in Diabetes Care and titled “Sodium–Glucose Cotransporter-2 Inhibitors, Glucagon-Like Peptide-1 Receptor Agonists, and Frailty Progression in Older Adults With Type 2 Diabetes”, examined a large national cohort of older adults in the United States who had recently begun different classes of diabetes medication.
The investigators analysed a 7 per cent sample of Medicare claims data, enabling real-world tracking of over one year of health outcomes. Frailty progression was assessed using a validated claims-based Frailty Index (CFI), which ranges from 0 to 1 and reflects the cumulative presence of age-related health deficits. Higher CFI scores indicate more severe frailty.
Key findings – slower frailty progression with SGLT-2 and GLP-1 therapies
Older adults newly prescribed a GLP-1 receptor agonist, such as semaglutide (Ozempic) or liraglutide (Victoza), demonstrated a mean CFI change of –0.007 (95 per cent CI: –0.011 to –0.004) compared with matched new users of DPP-4 inhibitors. Those initiating SGLT-2 inhibitors, including empagliflozin (Jardiance) and dapagliflozin (Farxiga), experienced a mean change of –0.005 (95 per cent CI: –0.008 to –0.002).
These figures represent a statistically significant slowing in frailty progression over the study period. In contrast, people beginning sulfonylureas did not show a meaningful difference relative to DPP-4 inhibitor users.
Importantly, the study found that cardiovascular events and other safety-related health issues explained only a small proportion of the protective association. This suggests that these classes of medications may exert a more direct biological effect on mechanisms related to frailty, such as inflammation, physical function, or metabolic stress.
Why frailty matters in older adults with type 2 diabetes
Frailty is common among older adults and especially prevalent in people living with type 2 diabetes. Previous research indicates that 10–15 per cent of adults over the age of 65 meet criteria for frailty, with substantially higher rates among those with diabetes. Multiple factors contribute to this increased vulnerability, including chronic low-grade inflammation, accelerated muscle loss, cardiovascular disease, and the overall physiological strain of managing a long-term condition.
Frailty is linked to an elevated risk of falls, disability, hospital admission, diminished quality of life, and reduced survival. Because frailty is difficult to reverse once it becomes established, clinicians and researchers have prioritised strategies that can delay or slow its progression. The study’s findings therefore hold particular significance for geriatric diabetes care.
Clinical implications – a possible shift in medication decision-making
The results may encourage clinicians to consider the broader health trajectory of older adults when selecting diabetes medications, especially as SGLT-2 inhibitors and GLP-1 receptor agonists are increasingly used for combined glycaemic, cardiovascular, and renal protection.
Chanmi Park, MD, MPH, the study’s lead author and Assistant Scientist I at the Hinda and Arthur Marcus Institute for Aging Research at Hebrew SeniorLife, highlighted this point:
“While SGLT-2 inhibitors and GLP-1 receptor agonists are primarily prescribed for blood sugar control and heart protection, our findings show they may also help older adults with diabetes stay stronger and less vulnerable to health setbacks. Because frailty is common, serious, and hard to reverse, this could meaningfully change how clinicians think about medication choices for ageing patients.”
A promising step towards more holistic diabetes care
The study adds to a growing body of literature suggesting that newer diabetes medications may offer multidimensional benefits. By potentially supporting physical resilience in addition to metabolic and cardiovascular health, SGLT-2 inhibitors and GLP-1 receptor agonists could become central tools in promoting healthier ageing for people living with type 2 diabetes.
Further research will be needed to better understand the biological mechanisms at play and to determine whether similar benefits appear in more diverse patient populations and longer-term studies.
CCH insight:
The results of this study are very encouraging from the perspective of GLP-1 medications and muscle mass/strength. There are currently concerns in some quarters about potential excess loss of muscle mass and sarcopenia accompanying weight loss from these drugs. However, this study points towards a positive impact on physical strength and function from GLP-1 therapy.
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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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WHO Issues First Global Guideline on GLP-1 Therapies for Treating Obesity
Key Takeaways:
- WHO has released its first global guideline on the use of GLP-1 therapies for treating obesity as a chronic, relapsing disease, offering conditional recommendations for adults.
- While the medicines show meaningful benefits, WHO stresses that medication alone will not reverse the obesity crisis and that person-centred, lifelong care is essential.
- Concerns remain about long-term safety data, affordability, availability, and the potential for widening global health disparities without deliberate policy action.
Introduction: A new milestone in global obesity care
The World Health Organization (WHO) has issued its first global guideline on the use of Glucagon-Like Peptide-1 (GLP-1) therapies for treating obesity, a chronic and relapsing disease affecting more than one billion people worldwide. Obesity contributes to 3.7 million deaths globally each year, and without urgent action the number of people living with obesity is projected to double by 2030.
The new guideline follows the decision made in September 2025 to add GLP-1 therapies to the WHO Essential Medicines List for managing type 2 diabetes in individuals at high risk. With this new document, WHO provides its first formal, conditional recommendations on the use of GLP-1 therapies specifically for obesity as part of a comprehensive treatment approach that includes healthy diets, regular physical activity, and professional health support.
“Obesity is a major global health challenge that WHO is committed to addressing by supporting countries and people worldwide to control it, effectively and equitably. Our new guidance recognises that obesity is a chronic disease that can be treated with comprehensive and lifelong care,” said Dr Tedros Adhanom Ghebreyesus, WHO Director-General. “While medication alone won’t solve this global health crisis, GLP-1 therapies can help millions overcome obesity and reduce its associated harms.”
The global and economic burden of obesity
Obesity is a complex, chronic disease and a major driver of noncommunicable conditions including cardiovascular diseases, type 2 diabetes, and some cancers. It also worsens outcomes for people who develop infectious diseases.
The global economic burden is profound. The worldwide cost of obesity is projected to reach US$ 3 trillion every year by 2030 due to increased healthcare demands and the rising costs of managing obesity-related complications. WHO hopes that clear guidance on the use of GLP-1 therapies will support efforts to reduce escalating healthcare expenditure while improving outcomes for people affected by obesity.
A landmark policy shift: WHO’s conditional recommendations
WHO’s new guideline sets out two key conditional recommendations based on currently available evidence.
1. Use of GLP-1 therapies in adults living with obesity
WHO states that GLP-1 therapies may be considered for long-term treatment in adults, excluding pregnant women. The medicines have demonstrated clear efficacy in supporting weight loss and improving metabolic outcomes. However, the recommendation remains conditional due to several concerns:
- Limited long-term data on safety, durability, maintenance, and outcomes following discontinuation
- High costs of treatment
- Insufficient readiness of health systems to support widespread use
- Possible negative effects on health equity
2. Combining GLP-1 therapies with intensive behavioural interventions
WHO also recommends that adults living with obesity and prescribed GLP-1 therapies may be offered structured behavioural interventions, including support for dietary changes and increased physical activity. This recommendation reflects low-certainty evidence suggesting that combining medication with lifestyle interventions may yield better outcomes.
Medication alone will not reverse the obesity crisis
Although GLP-1 therapies represent the first highly effective pharmacological treatment for adults living with obesity, WHO emphasises that medication on its own is insufficient. Obesity must be addressed as both an individual and societal challenge. The guideline calls for a fundamental shift toward comprehensive strategies built on three pillars:
- Creating healthier environments through population-level policies that promote health and prevent obesity.
- Protecting people at high risk by using targeted screening and structured early interventions.
- Ensuring person-centred, lifelong care for people living with obesity, recognising the chronic nature of the disease.
Implementing the guideline: Equity, system readiness and global access
WHO notes that fair access to GLP-1 therapies must be prioritised. Without deliberate policies, these medicines could deepen existing global health inequalities. System readiness, affordability, and supply capacity are major concerns.
Even with rapid increases in manufacturing, GLP-1 therapies are expected to reach fewer than 10 percent of people who could benefit from them by 2030. WHO urges global leaders to consider approaches that expand access, such as:
- Tiered pricing
- Pooled procurement mechanisms
- Voluntary licensing arrangements
These measures could help prevent widening disparities as demand expands.
Development of the guideline
The guideline was developed in direct response to requests from WHO Member States seeking actionable direction on obesity care. The process involved:
- Extensive assessment of available scientific evidence
- Input from global stakeholders
- Engagement with people who have lived experience of obesity
This document forms a core component of the WHO acceleration plan to stop obesity and will be updated regularly as new evidence emerges.
During 2026, WHO intends to work with partners to create a transparent and equitable prioritisation framework to ensure that individuals with the greatest medical need receive treatment first.
Notes to editors
About GLP-1 therapies for obesity
WHO defines obesity in adults as having a Body Mass Index (BMI) of 30 or above. GLP-1 receptor agonists help lower blood glucose, support weight loss, reduce cardiovascular and renal risks, and can reduce early mortality in people with type 2 diabetes.
This guideline provides recommendations for three GLP-1 agents used in the long-term treatment of obesity in adults:
- Liraglutide
- Semaglutide
- Tirzepatide
Falsified and substandard products
The surge in global demand has contributed to the spread of falsified and substandard GLP-1 products. WHO stresses that safe access requires:
- Prescription and distribution through regulated, qualified healthcare providers
- Strong oversight and monitoring
- Patient education
- International cooperation to safeguard public health
The organisation warns that falsified or substandard medicines threaten both patient safety and public trust.
CCH insight:
This new guideline is very welcome. The World Health Organisation has been a little slow in recognising obesity as a chronic relapsing disease and the importance of GLP-1 medications as a very important development in obesity treatment. However, these guidelines are comprehensive, consistent with treatment of obesity as a chronic relapsing disease, and recognise the challenges of delivering safe, sustainable, equitable obesity care.
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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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UMass Chan Launches National Collaborating Centre to Study Digital Lifestyle Interventions for People Using GLP-1 Medications
Key Takeaways:
- A major trial at UMass Chan will test whether a digital lifestyle change programme enhances outcomes for people using GLP-1 therapies to manage obesity, diabetes or cardiovascular disease.
- The work launches a new CDC-funded centre dedicated to lifestyle change implementation research, with a four-year award of 2 million dollars.
- Researchers aim to strengthen scientific evidence on how structured lifestyle interventions can support people taking GLP-1 medicines in real-world settings, including effects on physical activity, diet, muscle mass, adherence and quality of life.
Launch of a new national collaborating centre
UMass Chan Medical School has initiated a large research programme to examine whether a digital lifestyle change intervention can improve outcomes for people using GLP-1 therapies to manage obesity, diabetes or cardiovascular disease. This project marks the launch of the Lifestyle Change Implementation Research Network Collaborating Center at UMass Chan’s Prevention Research Center. The centre is supported by a four-year, 2 million-dollar award from the United States Centers for Disease Control and Prevention.
The project is jointly led by Jamie Faro, PhD, assistant professor of population and quantitative health sciences, and Stephenie C. Lemon, PhD, the Barbara Helen Smith Chair in Preventive and Behavioural Medicine, professor of population and quantitative health sciences, chief of the Division of Preventive and Behavioural Medicine, and co-director of the Prevention Research Center at UMass Chan.
Understanding the early experience of people using GLP-1 therapies
Dr Faro said: “We are going to look at what patients using GLP-1s are experiencing from early on in their journey, including changes in physical activity, diet, skeletal muscle mass, side-effect management, medication adherence and quality of life. We are hopeful this study addresses how lifestyle change interventions can impact these areas when implemented alongside patient’s medication.”
The research team intends to evaluate how a structured, digitally delivered programme may support people who are navigating the rapid physiological and behavioural changes often associated with GLP-1 therapy.
Study design and participant experience
Recruitment is expected to begin in early 2026, focusing on people living in the Worcester area. The study will enrol 220 participants and compare outcomes for individuals using the Noom Weight digital lifestyle change programme and Noom’s GLP-1 Companion with those receiving standard care. People who are allocated to standard care will have the option of accessing the digital intervention once the study concludes.
Participants in both groups will receive a wearable device to monitor physical activity over an eight-month period. They will also complete a series of lifestyle and health questionnaires, including dietary recalls. The dietary assessments will be led by co-investigator Sabrina Noel, PhD, RD, associate professor of biomedical and nutritional sciences and director of the Center for Population Health and the Health Assessment Laboratory at UMass Lowell.
Building the evidence base for real-world practice
Dr Faro emphasised the lack of robust data on how structured lifestyle change programmes can support people in real-world settings. She said: “There needs to be more scientific evidence on how lifestyle change interventions can support patients’ needs in real-world settings. The team laid the groundwork for this project by conducting pilot projects in UMass Memorial Health clinics, funded by the UMass Chan Ambulatory Research Consortium and the Mel Cutler pilot award in the Department of Population and Quantitative Health Sciences.”
The project will also investigate how lifestyle interventions can be implemented across different levels of the health system, including within clinical settings and by providers and payors.
Addressing risks and supporting long-term needs
Dr Lemon highlighted the importance of ensuring people using GLP-1 therapies receive appropriate lifestyle support. She said: “We want to establish evidence that can be applicable in other contexts that helps patients understand and engage in these necessary lifestyle interventions. Otherwise, we are going to have a population of GLP-1 users who lose weight but lose their muscle mass or have other issues that could be helped with lifestyle interventions, or who come off these meds and need additional support as they regain weight.”
A national network with shared goals
UMass Chan is one of four funded sites to receive a Lifestyle Change Interventions Research Network Coordinating Center Special Interest Project award from the CDC. The other sites include the University of Utah, the University of Pittsburgh and the University of South Carolina. Each site is conducting its own research project tailored to the evidence gaps identified by the CDC and to the needs of its local population.
The new centre at UMass Chan will collaborate closely with the CDC’s Coordinating Center and with Prevention Research Centers across the national network. Together they aim to advance research and practical implementation, with a focus on sustainable, evidence-based lifestyle change interventions to reduce obesity, diabetes, cardiovascular disease and related chronic conditions.
Dr Lemon summarised the broader ambition of the network: “The goal of the network is to bring together researchers and practitioners from across the country who are interested in this field, with a goal of building knowledge and capacity for implementing advanced weight loss interventions and potentially doing small scale additional research studies that fill evidence gaps in partnership between researchers and practitioners.”
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Novo Nordisk’s Oral Semaglutide Shows Cardiovascular Benefits Comparable to Wegovy Injection
Key Takeaways:
- Novo Nordisk’s new oral semaglutide 25 mg pill improved blood glucose control and reduced cardiovascular risk factors, matching the effects of its injectable counterpart, Wegovy.
- Data from the OASIS 4 trial showed significant weight loss and normalisation of blood glucose in people with prediabetes.
- The company expects U.S. regulatory approval for the first oral GLP-1 treatment for weight management by the end of 2025.
Oral GLP-1 pill shows comparable benefits to injection
Novo Nordisk has presented new findings suggesting that its experimental oral obesity medication delivers cardiovascular and metabolic benefits similar to those achieved with its blockbuster injectable, Wegovy. The results were shared at the ObesityWeek 2025 conference in Atlanta and strengthen the Danish company’s case for approval of the pill in the United States later this year.
The oral semaglutide 25 mg tablet, part of the company’s glucagon-like peptide-1 receptor agonist (GLP-1RA) portfolio, was shown to improve blood sugar regulation and reduce cardiovascular risk factors. These results could mark a milestone in obesity care, as the pill would become the first oral GLP-1 therapy approved for weight management.
OASIS 4 trial results
The data come from the OASIS 4 clinical trial, which compared oral semaglutide 25 mg with placebo in adults with overweight or obesity. After 64 weeks, 71.1% of participants with prediabetes who received the treatment achieved normal blood glucose levels, compared with 33.3% in the placebo group.
Participants who lost at least 15% of their body weight experienced additional health benefits, including reductions in blood pressure, inflammatory markers, and triglycerides. Overall, the trial demonstrated both significant weight loss and improvements in cardiometabolic health outcomes.
The primary OASIS 4 results, published in September in the New England Journal of Medicine, reported an average weight loss of 16.6% among participants taking the oral semaglutide.
Comparable outcomes with Wegovy injection
An indirect comparison between OASIS 4 and Novo Nordisk’s earlier STEP 1 trial, which evaluated injectable semaglutide (Wegovy), found the two formulations delivered comparable outcomes in weight reduction and improvements across key cardiometabolic markers.
These findings suggest that people who prefer not to use injectables could soon have an equally effective oral alternative. As demand for obesity pharmacotherapy continues to rise, an oral formulation may further expand access and adherence to GLP-1 treatments.
Regulatory outlook and market plans
The U.S. Food and Drug Administration (FDA) accepted Novo Nordisk’s application for oral Wegovy in May and is expected to deliver a decision by the end of the fourth quarter of 2025. The company has stated that, if approved, it intends to launch the product shortly thereafter.
Despite a recent dip in share price and slower sales growth, Novo Nordisk’s prospects have been buoyed by positive trial outcomes and an improved pricing arrangement under Medicare. The company is also undergoing leadership changes, including a new Chief Executive Officer and a restructured board, amid efforts to stabilise growth.
Novo Nordisk has indicated that, once approved, the pill will be made available through telehealth platforms such as Ro and WeightWatchers, with a potential subscription model offering discounted pricing. Additionally, Hims & Hers Health recently confirmed it is in discussions with Novo to provide both injectable and oral forms of Wegovy through its digital platform.
A step forward in accessible obesity care
If approved, Novo Nordisk’s oral semaglutide could redefine accessibility and adherence in obesity care. The convenience of a pill that matches the efficacy of an injectable treatment offers a compelling new option for people managing obesity and related cardiometabolic risks.
By broadening the range of treatment modalities within the GLP-1 class, Novo Nordisk continues to shape the evolving landscape of obesity pharmacotherapy — a field that is rapidly transforming the management of metabolic health worldwide.
CCH insights
This news about oral semaglutide is very welcome, but shouldn’t come as a surprise. Oral semaglutide is the exact same compound as injectable semaglutide, and as long as the dose administered orally is sufficient to deliver a similar blood concentration as the injectable form, then the effects should be very similar. It’s the same drug, just a cheaper and easier, but less efficient, route of administration.
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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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GLP-1 Receptor Agonists May Reduce Rheumatoid Arthritis Activity and Cardiovascular Risk in People with Obesity
Key Takeaways:
- GLP-1 receptor agonists were linked to reduced rheumatoid arthritis (RA) disease activity and improved cardiovascular risk factors in people with obesity or overweight.
- Significant improvements were observed in inflammation markers, weight, and cholesterol levels over 12 months of treatment.
- Findings suggest GLP-1RAs could offer dual benefits by addressing both metabolic and inflammatory disease processes in RA.
GLP-1RAs show promise in managing RA and cardiometabolic health
The use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) was associated with improvements in both rheumatoid arthritis (RA) disease activity and cardiovascular risk factors among people living with overweight or obesity, according to new research published in ACR Open Rheumatology.
Rheumatoid arthritis frequently coexists with obesity, which is known to exacerbate systemic inflammation, increase disease activity, and reduce response to treatment. Although GLP-1RAs are well established for treating obesity, type 2 diabetes, and for reducing cardiovascular risk, their potential role in inflammatory diseases such as RA has not been clearly defined.
Study overview
Researchers at the University of California, Los Angeles (UCLA) conducted a single-centre, retrospective observational study involving people with RA and a body mass index (BMI) of at least 27 kg/m². Participants were prescribed either semaglutide (oral or subcutaneous) or tirzepatide (subcutaneous) between 2018 and 2024.
Out of 554 screened individuals, 229 met the inclusion criteria. Of these, 173 took the prescribed GLP-1RA and formed the treatment cohort, while 42 individuals served as controls, having been prescribed but not initiating therapy. Participants were evaluated at 3-month intervals for up to 12 months.
Baseline characteristics
Both groups were broadly similar in terms of BMI, RA duration, and the use of conventional, biologic, or targeted synthetic disease-modifying antirheumatic drugs (DMARDs). However, diabetes (49% vs 14%) and hypertension (57% vs 38%) were more common in the treatment group.
The mean baseline BMI was 37.1 kg/m² among those receiving treatment and 35.3 kg/m² among control individuals. A greater proportion of participants in the treatment group were White (71% vs 47%).
Improvements in RA and cardiometabolic outcomes
People who took GLP-1RAs showed significantly greater improvements in several clinical measures compared with those who did not initiate therapy:
- RA disease activity scores: decreased by −0.03 versus an increase of +0.21 in controls (P = .03)
- Visual analogue scale (VAS) pain scores: decreased by −0.6 cm versus an increase of +1.3 cm in controls (P < .001)
- Weight: reduced by −6.2 kg versus −1.7 kg (P < .001)
- Total cholesterol: decreased by −10.3 mg/dL versus +0.3 mg/dL (P = .04)
- HbA1c: reduced by −0.4% versus +0.1% (P = .03)
Within the treatment group, significant reductions were also noted in inflammatory and lipid parameters, including:
- Erythrocyte sedimentation rate (ESR): −5.4 mm/hr (P = .004)
- C-reactive protein (CRP): −0.9 mg/dL (P = .004)
- Low-density lipoprotein (LDL) cholesterol: −7.3 mg/dL (P = .002)
- Triglycerides: −10.5 mg/dL (P = .004)
Tolerability and limitations
Adverse effects were relatively common, with 29% of participants discontinuing treatment, most frequently due to gastrointestinal symptoms or insurance-related issues.
Sensitivity analyses that accounted for comorbidities and serostatus did not significantly alter the study’s outcomes. However, researchers noted several limitations, including the single-centre, retrospective design, reliance on chart abstraction rather than validated disease activity indices, and the possibility of residual confounding.
Clinical implications
“Going forward, clinicians may consider integrating GLP-1RAs into the treatment regimens for patients with [RA and obesity], not only to target obesity-related complications but also possibly to target the underlying inflammatory disease process,” the authors concluded.
Some study authors disclosed affiliations with biotechnology, pharmaceutical, and medical device companies. A full list of disclosures is available in the original publication.
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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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GLP-1 Medications Should Be First-Line Treatment for Obesity, Say European Experts
Key Takeaways:
- European experts recommend semaglutide and tirzepatide as the preferred first-line medications for treating obesity and related complications.
- The new European Association for the Study of Obesity (EASO) guideline highlights tailored drug choices for specific obesity-linked conditions, such as heart disease, osteoarthritis, and sleep apnoea.
- Authors emphasise that managing obesity extends beyond weight loss, encompassing mental health, physical fitness, and quality of life.
New guidelines mark a turning point in obesity care
Two of the most widely prescribed weight-loss medications – semaglutide and tirzepatide – should now be considered the first treatment option for people living with obesity and associated complications, according to new guidance issued by the European Association for the Study of Obesity (EASO).
The guideline, published in Nature Medicine, identifies semaglutide, the active compound in Novo Nordisk’s Wegovy and Ozempic, and tirzepatide, marketed as Zepbound and Mounjaro by Eli Lilly, as highly effective and clinically appropriate first-line treatments for most cases requiring substantial weight reduction.
When only moderate weight loss is needed, other pharmacological options may be suitable. These include liraglutide, an earlier and less potent medication from the same class, as well as naltrexone–bupropion and phentermine–topiramate.
Although the recommendations are non-binding for European nations, they signal a major shift in the medical management of obesity across the continent.
Transforming obesity care
“Semaglutide, tirzepatide, and other drugs from the class known as GLP-1 agonists are completely transforming care of obesity and its complications,” said co-author Dr Andreea Ciudin of Vall d’Hebron University Hospital in Barcelona.
Dr Ciudin noted that while no single treatment algorithm can replace the nuanced clinical judgement of healthcare professionals, the new guidance is intended to support evidence-based decision-making and improve the consistency of obesity care across Europe.
Tailoring treatments to specific conditions
To develop the recommendations, the EASO guideline authors reviewed previous clinical trial data assessing medication efficacy, safety, and impact in individuals with obesity-related comorbidities.
The panel determined that tirzepatide should be prioritised for those experiencing obstructive sleep apnoea, whereas semaglutide should be considered first for individuals with knee osteoarthritis.
For people with metabolic or immune-related complications, the recommendations include semaglutide as a preferred option for those with existing cardiovascular disease or a history of stroke, tirzepatide for individuals with non-alcoholic fatty liver disease, and either drug for those with prediabetes or type 2 diabetes.
GLP-1 receptor agonists were initially developed to manage type 2 diabetes but have since shown remarkable efficacy in promoting sustained weight reduction and improving obesity-related outcomes.
Balancing costs and benefits
The guideline acknowledges that GLP-1 drugs are expensive and that economic considerations are complex. However, the authors argue that health systems should account for the long-term costs of untreated obesity.
“The cost of not treating obesity at early stages, thus enabling the progression to complications and end-organ damage, should be weighed equally in health policy and clinical decision-making,” the guideline authors wrote.
They added that effective obesity management should not be confined to weight loss alone but should also prioritise mental well-being, physical fitness, social participation, and quality of life.
Emerging evidence and ongoing updates
The authors acknowledged that many newer medications have not yet been evaluated for the treatment of individual complications. Nevertheless, the consistent association between weight reduction and improvements in related conditions supports their broader therapeutic potential.
According to the guideline, there is growing evidence that GLP-1 receptor agonists may also benefit individuals with chronic kidney disease, neurodegenerative conditions, polycystic ovary syndrome, certain cancers, and mental health disorders.
“Given the rapid advances in the field of medications to treat obesity, EASO intends to update the present treatment algorithm regularly to incorporate the latest available evidence,” said Professor Volkan Yumuk, President of EASO and Professor at Istanbul University–Cerrahpaşa.
Lifestyle interventions remain essential
The EASO guidance complements a June advisory jointly issued by the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. That advisory stressed that pharmacological treatment should always be combined with lifestyle and nutritional interventions.
“Although GLP‐1s alone can produce significant weight reduction and related health benefits, several challenges limit its long‐term success for individuals and populations,” the advisory stated.
It cited factors such as gastrointestinal side effects, nutrient deficiencies, muscle and bone loss, high costs, frequent discontinuation, and the risk of weight regain.
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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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