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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Bariatric Surgery Delivers Greater Long-Term Benefits Than GLP-1 Medicines Alone, Cleveland Clinic Study Finds
Key Takeaways:
- People with obesity and type 2 diabetes who underwent bariatric surgery lived longer and experienced fewer serious complications than those treated with GLP-1 receptor agonist medicines alone.
- Surgery was associated with a lower risk of death, cardiovascular disease, kidney disease, and diabetes-related eye damage over a 10-year period.
- Patients who had surgery lost more weight, achieved better blood sugar control, and relied less on medications for diabetes, blood pressure, and cholesterol.
Major Cleveland Clinic study compares treatments
A large-scale study conducted by Cleveland Clinic has shown that people living with obesity and type 2 diabetes who undergo bariatric (metabolic) surgery experience significantly better long-term outcomes compared with those treated only with GLP-1 receptor agonist (GLP-1RA) medicines.
The research, published in Nature Medicine, followed nearly 4,000 patients and found that surgery was linked to longer life expectancy, greater weight loss, improved blood sugar control, and reduced reliance on diabetes and cardiovascular medicines.
“Even with today’s best medicines, metabolic surgery offers unique and lasting benefits for people with obesity and diabetes,” said Ali Aminian, M.D., Director of Cleveland Clinic’s Bariatric & Metabolic Institute and primary investigator of the study. “The benefits we observed went beyond weight loss. Surgery was linked to fewer heart problems, less kidney disease and even lower rates of diabetes-related eye damage.”
Study design and findings
The M6 study (Macrovascular and Microvascular Morbidity and Mortality after Metabolic Surgery versus Medicines) included 3,932 adults with both diabetes and obesity who received care at Cleveland Clinic over a period of up to 10 years.
- 1,657 participants underwent metabolic surgery, including gastric bypass or sleeve gastrectomy.
- 2,275 participants were treated with GLP-1 medicines such as liraglutide, dulaglutide, exenatide, semaglutide, and tirzepatide.
The median follow-up was 5.9 years (interquartile range 4.4–7.6 years).
Key outcomes:
At the 10-year mark, patients who underwent metabolic surgery had significantly better outcomes:
- 32% lower risk of death
- 35% lower risk of major adverse cardiovascular events (MACE), including heart attack, heart failure, or stroke
- 47% lower risk of chronic kidney disease (CKD)
- 54% lower risk of diabetes-related retinopathy (eye damage)
The 10-year cumulative incidence of all-cause mortality was 9.0% (95% CI 6.8–10.8%) in the metabolic surgery group, compared with 12.4% (95% CI 9.9–15.2%) in the GLP-1RA group (adjusted hazard ratio 0.68, 95% CI 0.48–0.96; P = 0.028).
The 10-year cumulative incidence of MACE was 23.7% (95% CI 20.0–27.6%) in the metabolic surgery group and 34.0% (95% CI 28.1–44.2%) in the GLP-1RA group (adjusted hazard ratio 0.65, 95% CI 0.51–0.82; P < 0.001).
On average:
- People who had surgery lost 21.6% of their body weight over 10 years.
- People treated with GLP-1 medicines lost 6.8% of their body weight.
- Haemoglobin A1c (HbA1c), a key marker of average blood sugar, improved by -0.86% with surgery compared with -0.23% with GLP-1 medicines.
In addition, surgery patients required fewer prescriptions for diabetes, blood pressure, and cholesterol management.
Expert perspectives
The findings underscore the long-term advantages of bariatric surgery even in the current era of advanced GLP-1 treatments.
“Even in the era of these powerful new drugs to treat obesity and diabetes, metabolic surgery may provide additional benefits, including a survival advantage,” said Steven Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic and senior author of the study.
Dr Aminian emphasised the importance of maintaining surgery as a treatment option:
“Our findings indicate that surgery should remain an important treatment option for obesity and diabetes. These long-term benefits are harder to achieve with GLP-1 medicines alone, as many patients stop using the medications over time.”
Study limitations and future research
The authors highlighted that the study was observational, not a randomised controlled trial. This means that while strong associations were observed, direct comparisons may be influenced by unmeasured factors.
In addition, the study did not focus exclusively on the most recent and highly effective GLP-1 medicines. The authors noted that future trials should directly compare metabolic surgery with newer GLP-1 therapies, such as semaglutide and tirzepatide, to help guide clinical decision-making.
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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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Higher Dose of Semaglutide Delivers Greater Weight Loss and Metabolic Improvements
Key Takeaways:
- Tripling the standard dose of semaglutide led to significantly greater weight loss and improved metabolic outcomes, without an increase in serious adverse effects.
- Participants on the higher dose achieved clinically meaningful reductions in body weight, waist circumference, and HbA1C levels, with nearly one-third losing 25% or more of their starting weight.
- Side effects were mostly mild and transient, suggesting that the higher dose may be a safe option for people requiring more intensive obesity treatment.
Landmark findings from the STEP UP trials
Tripling the standard dose of semaglutide – a widely prescribed glucagon-like peptide-1 receptor agonist (GLP-1RA) – resulted in markedly greater weight loss and cardiometabolic benefits, according to results from two large multicentre clinical trials led by UT Southwestern Medical Center. The studies, published in The Lancet Diabetes & Endocrinology, indicate that patients may be able to safely take a higher semaglutide dose than currently approved if they need to lose additional weight.
“Semaglutide and other drugs in its class have been life-changing for people living with obesity around the world. Our new findings suggest that increasing the dose can lead to even greater benefits and may be appropriate for some patients,” said study leader Dr Ildiko Lingvay, Professor of Internal Medicine in the Division of Endocrinology and in the Peter O’Donnell Jr. School of Public Health at UT Southwestern.
Context: The global obesity challenge
Obesity affects nearly one billion people worldwide, according to the World Health Organization, and is a major driver of conditions such as Type 2 diabetes, cardiovascular disease, certain cancers, and liver disease. GLP-1RAs, first authorised in the early 2000s, have transformed the management of Type 2 diabetes and, more recently, chronic weight management and cardiovascular risk reduction.
Semaglutide received approval from the US Food and Drug Administration (FDA) in 2017 for people with Type 2 diabetes and has since been approved at a 2.4 mg weekly dose for weight management in both the United States and European Union. While this dose can produce significant weight loss, many patients do not achieve their treatment goals.
The STEP UP trials: Design and participants
To explore whether higher doses could deliver additional benefits, researchers conducted two phase 3b clinical trials – STEP UP Diabetes and STEP UP Obesity – to compare the effects of a weekly 7.2 mg dose of semaglutide with the standard 2.4 mg dose and placebo.
In the STEP UP Diabetes trial, 512 adults with both obesity and Type 2 diabetes were randomly assigned to three groups:
- 307 participants received 7.2 mg semaglutide weekly.
- 103 participants received 2.4 mg semaglutide weekly.
- 102 participants received placebo.
Participants were followed for 72 weeks at 68 trial sites across eight countries in Europe, southern Africa, and North America, including UT Southwestern. All participants received counselling every four weeks to encourage reduced-calorie diets and increased physical activity.
Results: Substantial weight loss and metabolic gains
Weight loss outcomes
As seen in earlier studies, the standard 2.4 mg dose produced a mean weight loss of 10.4% of starting weight, compared with 3.9% in the placebo group. However, participants taking the higher 7.2 mg dose achieved an even greater mean weight loss of 13.2%.
In addition, those receiving 7.2 mg were significantly more likely to:
- Reach a 20% reduction in waist circumference – a key measure of cardiometabolic health.
- Achieve superior improvements in HbA1C, an indicator of blood sugar control.
Outcomes in people without type 2 diabetes
The STEP UP Obesity trial, which focused on people with obesity but without Type 2 diabetes, showed even more striking results. Nearly one-third of participants on the higher dose lost 25% or more of their starting weight, compared with 15% of those on the standard dose and none on placebo.
Safety profile and side effects
The most frequently reported side effects were gastrointestinal symptoms, such as nausea, diarrhoea, and constipation. These affected approximately half of participants taking semaglutide and about a quarter of those on placebo. Most symptoms occurred during the dose-escalation period and tended to diminish over time.
The only side effect reported more frequently in the higher dose group was dysaesthesia (a change in touch sensation), experienced by approximately 20% of participants taking 7.2 mg, compared with 5% of those on the lower dose. Importantly, there was no increase in serious adverse events associated with the higher dose.
“These findings reinforce the promise of semaglutide and other GLP-1RAs, with benefits that appear to increase at higher doses without compromising patient safety,” Dr Lingvay concluded.
Funding and disclosures
Both STEP UP trials were funded by Novo Nordisk A/S, the manufacturer of semaglutide. Dr Lingvay reports receiving personal consulting fees from Novo Nordisk.
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Weight loss medications linked to major reductions in heart failure hospitalisations and death
Key Takeaways:
- People with heart failure with preserved ejection fraction (HFpEF), obesity, and Type 2 diabetes who were prescribed semaglutide or tirzepatide had over 40 per cent lower risk of hospitalisation or death compared with those taking sitagliptin.
- Researchers analysed real-world data from more than 90,000 patients, making this the largest study to date on GLP-1 medications in HFpEF.
- Findings suggest semaglutide and tirzepatide could become a new treatment option for heart failure, though they are not yet approved for this use.
A new avenue for treating a difficult condition
A major new study has found that weight loss drugs semaglutide and tirzepatide may significantly reduce the risk of hospitalisation and death among people living with heart failure with preserved ejection fraction (HFpEF), obesity, and Type 2 diabetes.
The research, conducted by investigators at Harvard-affiliated Mass General Brigham (MGB), showed that initiating either of the two medications was linked to an over 40 per cent reduction in the combined risk of being hospitalised with heart failure or dying from any cause, compared with patients who received a placebo by proxy.
HFpEF is a common form of heart failure in which the heart muscle becomes thick and stiff. Although the pumping function remains intact, the heart cannot fill adequately with blood, leaving the body’s organs and tissues under-supplied. HFpEF disproportionately affects people with obesity and Type 2 diabetes, and current treatment options remain limited.
“Despite the widespread morbidity and mortality burden of HFpEF, current treatment options are limited,” said corresponding author Nils Krüger of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital and a postdoctoral research fellow at Harvard Medical School. “Both semaglutide and tirzepatide are well-known for their effects on weight loss and blood sugar control, but our study suggests they may also offer substantial benefits to patients with obesity and Type 2 diabetes by reducing adverse heart failure outcomes.”
Largest analysis of GLP-1 medications in HFpEF
To strengthen the evidence base beyond small, randomised clinical trials, the research team examined real-world data from more than 90,000 people with HFpEF, obesity, and Type 2 diabetes. Findings, published in JAMA and presented at the European Society of Cardiology Congress, demonstrated a significant reduction in both heart failure hospitalisation and all-cause mortality among patients who began treatment with semaglutide or tirzepatide.
While previous trials of GLP-1 receptor agonists in obesity-related HFpEF showed promising results, they involved relatively small study populations. Regulatory agencies and professional societies have therefore not yet approved or endorsed the use of these medications for HFpEF.
To address this gap, the MGB team used three large United States insurance claims databases to emulate two earlier placebo-controlled trials, but with study populations that were on average 19 times larger.
Methodology and comparative effectiveness
The researchers compared the one-year risk of hospitalisation for heart failure or death among new users of semaglutide or tirzepatide with that of patients prescribed sitagliptin, a diabetes medication known not to affect HFpEF. This “active placebo” comparator allowed them to verify earlier clinical trial results in much larger and more representative groups of patients.
Overall, semaglutide and tirzepatide were each associated with more than 40 per cent lower risk of hospitalisation or death compared with sitagliptin. Both drugs demonstrated similar effectiveness in this context.
Importantly, both medications also maintained acceptable safety profiles in this real-world study, reinforcing findings from earlier clinical trials.
Future directions for research
Although the findings are compelling, GLP-1 receptor agonists are not currently licensed for the treatment of heart failure. The research team emphasised the need for further investigation to determine the long-term impact of these medications, to identify which subgroups of people with HFpEF may benefit the most, and to explore whether they also reduce additional cardiovascular risks beyond heart failure.
“By using nationwide data and an innovative methodological approach, our team was able to expand the findings of previous trials to larger populations more representative of HFpEF patients treated in clinical practice,” Krüger explained. “Our findings show that in the future, GLP-1 targeting medications could provide a much-needed treatment option for patients with heart failure.”
CCH Insight:
These are very positive results, and add to the evidence base for the benefits of GLP-1 medications for patients with HFpEF. It is an observational study, so large-scale clinical trials are needed to confirm these findings, but it probably won’t be long before GLP-1 medications are licensed for treatment of HFpEF, yet another condition to add to the growing list that can be treated with these drugs.
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GLP-1 receptor agonists linked to reduced risk of eye inflammation, Cleveland Clinic study shows
Key Takeaways:
- Researchers at the Cleveland Clinic Cole Eye Institute found that GLP-1 receptor agonist (GLP-1RA) therapy was associated with a significantly lower risk of developing non-infectious uveitis, an inflammatory eye condition that can cause permanent vision loss.
- Analysis of data from over 516,000 patients showed that people prescribed GLP-1RAs had about a 50 percent lower risk of new onset uveitis compared to those who had never taken these drugs.
- The findings suggest GLP-1RAs may have anti-inflammatory benefits beyond blood sugar and weight management, opening up the possibility of new protective applications in autoimmune and inflammatory eye diseases.
Understanding uveitis and its impact
Uveitis is an inflammatory condition that affects the uvea, the middle layer of the eye, and can extend to nearby structures such as the retina. Symptoms often include eye pain, redness, and blurred vision. In severe or untreated cases, uveitis can lead to irreversible vision loss. Globally, there are approximately 4 million new diagnoses every year.
The condition is primarily driven by inflammation inside the eye and is often associated with autoimmune or systemic inflammatory diseases, such as sarcoidosis, ankylosing spondylitis, and inflammatory bowel disease. Current treatments typically involve steroids, while people with chronic forms may require long-term immunosuppressive therapy.
Research overview
The Cleveland Clinic retrospective cohort study was published in JAMA Ophthalmology and conducted by researchers at the Cole Eye Institute. Using the TriNetX platform – a large-scale database containing de-identified electronic health records from more than 120 million patients across over 60 healthcare organisations – the team examined data spanning 2006 to 2025.
The study assessed records from 516,052 patients. This included:
- 258,026 patients prescribed GLP-1RA therapy (irrespective of whether they had diabetes).
- 258,026 matched controls who had never been prescribed a GLP-1RA but who may have used other diabetes treatments such as insulin or metformin.
The data was further analysed across four distinct cohorts:
- An overall cohort.
- Patients with diabetes.
- Patients with type 2 diabetes.
- Patients without diabetes.
Equal numbers of patients were included in the control groups for each cohort.
Findings and protective association
Primary analysis measured the risk of uveitis after the first GLP-1RA prescription, with further assessments carried out at one, three, and five years following treatment initiation.
In the overall cohort, GLP-1RA use was associated with a 51.7 percent relative risk reduction for newly diagnosed non-infectious uveitis. The protective effect was consistent across all subgroups, with people prescribed GLP-1RAs showing around a 50 percent lower risk compared to those who had never used these drugs.
Importantly, these results were observed when compared not only with the general control group but also with patients taking insulin or metformin, two commonly prescribed diabetes medications.
Implications for people at higher risk
Certain populations face a heightened risk of uveitis, including individuals with a family history, genetic predispositions, or those living with autoimmune diseases. For these groups, the findings carry particular significance.
“For patients in these populations who meet the indication for diabetic or weight loss medication, this research is promising because being prescribed GLP-1RAs may have the additional benefit of decreasing the risk of new onset non-infectious uveitis,” the authors noted.
Expert commentary
Dr Sumit Sharma, a retina and uveitis specialist at the Cleveland Clinic Cole Eye Institute and senior author of the study, emphasised the broader significance of the findings:
“This is the first study to find a protective effect of GLP-1RA therapy for autoimmune disease, which is very exciting and shows a further benefit of these drugs for patients beyond just weight loss and control of diabetes.”
Looking ahead
While further research is required to confirm and expand upon these findings, the study provides strong evidence that GLP-1RAs may offer benefits beyond glycaemic control and weight management. In addition to their established roles in type 2 diabetes and obesity care, these medications could potentially reduce the risk of inflammatory eye diseases such as uveitis.
This emerging evidence contributes to a growing understanding of the broader systemic effects of GLP-1RA therapy, highlighting its potential to reshape care for both metabolic and inflammatory conditions.
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GLP-1 receptor agonists linked to greater dementia risk reduction than metformin in people with type 2 diabetes
Key Takeaways:
- In people with type 2 diabetes, initiating GLP-1 receptor agonist therapy rather than metformin was linked to a 10% lower overall risk of dementia over two years.
- The largest benefits were observed for Alzheimer’s disease and other non-vascular forms of dementia, with reductions of 8% and 12%, respectively.
- Older adults and women appeared to experience greater protective effects from GLP-1 receptor agonists compared with men and younger individuals.
Study overview
A large retrospective analysis has found that among people with type 2 diabetes, those who newly began treatment with a glucagon-like peptide-1 (GLP-1) receptor agonist had a significantly lower risk of developing dementia compared with those who started metformin.
The study, published in BMJ Open Diabetes Research & Care, examined real-world health data over a two-year follow-up period. Overall dementia risk – defined as the first recorded diagnosis of vascular dementia, Alzheimer’s disease (AD), unspecified dementia, or dementia due to other diseases – was 2.4% in the GLP-1 receptor agonist group, compared with 4.8% in the metformin group, representing a 10% relative risk reduction.
Specific dementia outcomes
While the difference in vascular dementia risk between the two groups was not statistically significant (0.7% for GLP-1 receptor agonists versus 1.3% for metformin), there were clear benefits for other dementia types:
- Alzheimer’s disease – 1.2% incidence in GLP-1 receptor agonist users compared with 2.6% in metformin users, an 8% relative risk reduction.
- Other non-vascular dementias – 1.0% incidence in GLP-1 receptor agonist users versus 2.4% in metformin users, a 12% relative risk reduction.
“These findings address a key knowledge gap by directly comparing the neuroprotective efficacy of GLP-1 [receptor agonists] and metformin in dementia prevention,” write lead author Jiaqiang Zhang of The People’s Hospital of Zhengzhou University, Henan, China, and colleagues. “They provide actionable insights for clinical decision-making and may inform future guidelines.”
Possible neuroprotective mechanisms
Previous research has shown that both GLP-1 receptor agonists and metformin may exert neuroprotective effects, including:
- Reduction of neuroinflammation and oxidative stress
- Improved insulin sensitivity
- Enhanced cerebrovascular health
However, no earlier study had directly compared the two in terms of their potential cognitive benefits.
Study design and population
The researchers used the TriNetX global federated health network, which contains deidentified electronic health records from more than 98 healthcare organisations worldwide.
From this database, they identified more than 174,000 adults with type 2 diabetes who received a first-line prescription for either a GLP-1 receptor agonist or metformin between 2004 and 2024.
Propensity score matching created two equal groups – 87,229 participants in each – ensuring they were comparable in age (mean of around 58 years) and other baseline characteristics. Just under two-thirds of participants in each group were women.
Eligibility criteria included:
- Continuous prescription of the assigned medication for at least six months
- At least 24 months of follow-up data
Analyses were adjusted for factors such as age, sex, ethnicity, comorbidities (including hypertension, ischaemic heart disease, and cerebrovascular disease), metabolic measures (such as glycated haemoglobin and obesity), and other medication use.
Subgroup findings
The dementia risk reduction associated with GLP-1 receptor agonists was consistent across all subgroups analysed, with particularly strong effects in:
- Older adults – Those aged 60 years or older had a 15–20% lower overall dementia risk compared with metformin users.
- Women – Women had a greater reduction in dementia risk (adjusted hazard ratio [HR] 0.83) than men (HR 0.90).
Additional outcomes and limitations
The study also found a significant all-cause mortality benefit with GLP-1 receptor agonists compared to metformin, with cumulative mortality rates of 4.8% versus 8.8% (HR 0.89).
The authors acknowledged several limitations:
- Potential residual confounding despite propensity score matching and sensitivity analyses
- Possible misclassification of dementia subtypes or under-reporting of outcomes
- Exclusion of people with prior use of the study medications, which may limit generalisability to those with mixed treatment histories
Conclusions and next steps
The authors concluded:
“GLP-1 [receptor agonists] were more effective than metformin in reducing the risk of dementia – especially AD and non-vascular types – highlighting their potential as a preferred first-line treatment in [type 2 diabetes mellitus].”
They added: “Further randomised trials are warranted to validate these findings.”
CCH Insight:
This study provides further evidence for the neuroprotective effects of GLP-1RAs, and it is interesting to note that the effect was greater in non-vascular forms of dementia, suggesting these benefits are independent of the known cardiovascular benefits of these medications. It also supports the case for increased prescribing of GLP-1RAs as an alternative to metformin as a first-line treatment for type 2 diabetes – currently GLP-1RAs are generally considered a second or third choice of second-line treatment.
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Year-long support needed after stopping weight loss injections says NICE
Key Takeaways:
- NICE advises that people stopping GLP-1 receptor agonist weight loss injections should receive at least 12 months of structured follow-up support to help maintain weight loss and associated health benefits.
- Experts welcome the recommendation but warn that NHS capacity and resources may be insufficient to deliver consistent, nationwide “wraparound” care.
- Around 1.5 million people in the UK are thought to be using weight loss injections, with an estimated 240,000 expected to be offered tirzepatide (Mounjaro) on the NHS within the next three years.
NICE Urges Long-Term Support After Weight Loss Treatment
The National Institute for Health and Care Excellence (NICE) has updated its guidance to recommend that people who stop taking weight loss injections receive structured advice and ongoing support for at least a year. The aim is to ensure that the benefits achieved through treatment—both weight loss and related health improvements—are maintained over the long term.
NICE’s advice applies to people coming off glucagon-like peptide-1 receptor agonist (GLP-1RA) medications such as semaglutide (Wegovy) and tirzepatide (Mounjaro). These drugs work by mimicking the GLP-1 hormone, which helps regulate appetite and food intake.
Without continued support, the risk of regaining lost weight is high. Studies suggest that about four in five people who discontinue these medications regain the weight they lost once their prescription ends.
Implementation Challenges and NHS Capacity
While the update has been welcomed by obesity care experts, there is widespread concern about whether the NHS has the resources to deliver such long-term, structured follow-up.
Around 1.5 million people in the UK are estimated to be using weight loss injections, and NHS England plans to offer tirzepatide to approximately 240,000 people over the next three years. The scale of potential demand raises questions about the availability of trained staff, access to services, and consistency of care across different regions.
Almost one-third (29%) of adults in England have obesity, and 64% are categorised as overweight or obese. Obesity is estimated to cost the NHS £11.4 billion annually through its impact on related health conditions.
Details of the Guidance
NICE states that general practitioners (GPs) and specialist overweight and obesity services must have clear protocols for supporting people once their prescription ends or they are discharged from treatment. The support should be designed to help individuals maintain lifestyle changes, prevent weight regain, and preserve associated health benefits.
The recommended interventions may include practical advice from initiatives such as NHS Better Health, tailored strategies to adapt daily habits, and adjustments in home or work environments to support healthier choices.
NICE also advises that if a patient approaches their GP for similar guidance after using a weight loss drug obtained privately, the GP should provide appropriate support or make a referral. However, NICE notes that such cases are expected to be uncommon.
Expert Perspectives
Jonathan Benger, Deputy Chief Executive and Chief Medical Officer at NICE, emphasised the importance of continuity in care:
“Successful weight management doesn’t end when medication stops or when someone completes a behavioural programme. We know that the transition period after treatment is crucial, and people need structured support to maintain the positive changes they’ve made.”
Obesity UK welcomed the recognition of the need for ongoing care but expressed doubt about the NHS’s ability to implement it effectively. Alison Forster, Operations Manager at Obesity UK, commented:
“We remain concerned about the limited resourcing of NHS weight management services and the significant variability in access and provision across the country. This guidance just doesn’t go far enough.
Many of the people we support face long waits, inconsistent care pathways, and a lack of psychological and social support—issues that are not sufficiently addressed by the current system.
We know from existing evidence that about 80% of people will regain the weight once they come off the medication, and wraparound care is what is lacking after someone has stopped.”
Positive Direction but Further Reform Needed
Nicola Heslehurst, President of the Association for the Study of Obesity and an expert in maternal and child nutrition at Newcastle University, welcomed the move:
“It is a really positive move in the right direction to see the recognition that longer term support is required for managing obesity beyond short term programmes, whether these are medication or weight management programmes.”
However, she highlighted the need for structural changes in service commissioning:
“The lack of continued support has been a major flaw in service commissioning and delivery to date.”
The Role of General Practice and Broader Obesity Care
Kamila Hawthorne, Chair of the Royal College of General Practitioners, said:
“Patients will likely need support to sustain their weight loss once they stop taking the medication. As such, this is important and sensible guidance from NICE.
As a college we’ve been clear that whilst weight loss medications have significant potential benefits for patients who are struggling to lose weight, they mustn’t be seen as a ‘silver bullet,’ and ensuring access to sufficient ‘wraparound’ services—particularly for when patients come off their medication—will be key to optimal health outcomes. It’s vital that the rollout of weight loss medications as a treatment for obesity does not come at the expense of other weight loss services.”
Government Strategy
Expanding access to GLP-1RAs forms part of the UK government’s 10-year NHS plan to tackle obesity. This strategy aims not only to provide effective treatment options but also to integrate them within a broader system of ongoing care and prevention, ensuring that people who achieve weight loss have the resources to maintain it in the long term.
CCH Insight:
This new guidance from NICE seems, at first, like a sensible idea… until you think about how these drugs are meant to be used, and the evidence available for weight regain. GLP-1-based medications are meant to be used as an adjunct to diet and lifestyle support. So patients should be receiving the type of advice advocated by NICE whilst taking the drugs, not after they stop. By the time a patient stops taking the medication, they should have already established healthier eating and lifestyle habits.
If they have not done so by then, it is probably too late – because you are then asking people to eat more healthily just as their appetite and cravings are increasing after ceasing their medication. The other issue is that the current evidence, from clinical trials, suggests that lifestyle interventions DO NOT prevent weight regain after cessation of these drugs. NICE appear to be ignoring this evidence – why? Because the inconvenient truth is that obesity is a chronic relapsing condition, and many people with the condition may need to continue GLP-1 therapy for life if they are to maintain weight loss and health benefits it brings. NICE probably don’t like the implications of this in terms of cost, but it would actually save money in the long run through prevention of obesity-related complications.
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Updated Canadian guideline highlights expanded role of obesity medications
Key Takeaways:
- New Canadian recommendations highlight obesity pharmacotherapy as a safe, effective, and long-term treatment option, focusing on improving overall health rather than weight loss alone.
- The guideline moves away from sole reliance on body mass index (BMI), advocating a more individualised approach that incorporates multiple health indicators and personal treatment goals.
- Updated recommendations include new medicines such as tirzepatide and setmelanotide, and address obesity-related complications including cardiovascular disease, osteoarthritis, and heart failure with preserved ejection fraction.
Focus on Health, Not Just Weight Loss
“Pharmacotherapy can help people living with obesity improve overall health, not just lose weight,” says Dr Sue D Pedersen, MD, endocrinologist and obesity medicine specialist in Calgary, and lead author of the updated guideline. “The goal of obesity medications is to improve metabolic, mechanical, and/or mental health, and improve quality of life, incorporating treatment goals that are important to each individual patient.”
The updated recommendations reflect the evolving understanding of obesity as a complex, chronic disease that requires a personalised treatment approach. Rather than focusing solely on weight reduction, the guideline emphasises outcomes that matter most to each person, including improvements in energy, mobility, mental wellbeing, and the management of related health conditions.
Updated and Expanded Recommendations
This latest update introduces six new and seven revised recommendations, building on evidence published since the 2022 and 2020 versions of the guideline.
Key changes include:
- Recognition of new medications – tirzepatide and setmelanotide are now included as treatment options.
- Expanded scope – the guideline now addresses pharmacological approaches for obesity-related complications such as atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and osteoarthritis.
- Revised assessment criteria – moving away from BMI as the sole measurement, the guideline recommends using additional indicators such as waist circumference, waist-to-hip ratio, and waist-to-height ratio. These should be adjusted for sex and ethnicity where appropriate and interpreted alongside the presence of obesity-related complications.
Pharmacotherapy as a Core Pillar of Obesity Care
“Obesity pharmacotherapy is a safe and effective option to support long-term obesity care,” says Dr Pedersen. “It is one of three pillars of treatment outlined in the full Canadian Adult Obesity Clinical Practice Guideline, with other pillars being behavioural and psychological and surgical approaches. Obesity treatment should always be tailored to each person’s specific health needs, values, and preferences. Recommendations also support sustained use of obesity pharmacotherapy as part of a long-term strategy to maintain improvements in health and quality of life.”
This long-term strategy underscores the importance of maintaining health gains rather than viewing weight loss as a one-time intervention. By integrating medication into a comprehensive care plan, healthcare providers can help people sustain improvements in physical and mental health over time.
Safety and Quality Considerations
The guideline also cautions against the use of compounded obesity medications due to concerns about content, safety, efficacy, and quality. These risks highlight the importance of using approved medications with established quality controls and safety profiles.
CCH Insight:
This new guidance is very welcome, and reflects the rapid advances in this area of obesity treatment over the last few years. The recommendations should be applauded for several reasons. Firstly, the recognition that pharmacotherapy offers more than weight loss alone; it is an important tool in improving the overall health of people living with obesity, improving metabolic function, reducing cardiovascular disease risk and enhancing mental well-being, all tailored to the unique circumstances of each individual. Secondly, they emphasise the fact that these drugs are meant to be used as an adjunct to diet and lifestyle advice, not an alternative to it, which is a message that often seems to get lost in the hype around them. Thirdly, the use of central adiposity indicators (such as waist circumference) as well as BMI for assessing suitability for GLP-1 therapy, and finally the recommendation that these drugs be considered for anyone with a BMI > 30 (or the equivalent adjusted for ethnicity), with or without the presence of obesity-related conditions.
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GLP-1 drugs found to boost testosterone in men with obesity or diabetes
Key Takeaways:
- Anti-obesity medications significantly raised testosterone levels in men with obesity or type 2 diabetes.
- After 18 months of treatment, the percentage of men with normal testosterone levels increased from 53% to 77%.
- These medications may now be considered as part of broader reproductive health strategies for men with obesity or diabetes.
Introduction: A Link Between Obesity, Diabetes and Low Testosterone
Men living with obesity or type 2 diabetes frequently experience reduced testosterone levels, a condition associated with symptoms such as fatigue, diminished libido, and lower quality of life. A new study presented at ENDO 2025, the annual meeting of the Endocrine Society held in San Francisco, provides compelling evidence that anti-obesity medications may offer an effective intervention.
“While it is well known that weight loss from lifestyle changes or bariatric surgery increases testosterone levels, the impact that anti-obesity medications may also have on these levels has not been widely studied,” said Dr Shellsea Portillo Canales, endocrinology fellow at SSM Health St. Louis University Hospital. “Our study is among the first to provide compelling evidence that low testosterone can be reversed with the use of commonly prescribed anti-obesity medications.”
Study Design and Participant Profile
The research team conducted a retrospective analysis using electronic health records of 110 adult men diagnosed with obesity or type 2 diabetes. All participants were undergoing treatment with one of three commonly prescribed anti-obesity medications: semaglutide, dulaglutide or tirzepatide. Importantly, none of the men were receiving testosterone or other hormonal therapy at the time of the study.
Researchers measured both total and free testosterone levels before and during treatment, over an 18-month observation period.
Findings: Weight Loss and Hormonal Restoration
Over the course of treatment, participants achieved an average weight reduction of 10%. This weight loss was accompanied by a marked improvement in testosterone levels: the proportion of men with normal total and free testosterone levels rose from 53% at baseline to 77% at follow-up.
These outcomes suggest a dual benefit of anti-obesity medications – not only aiding in weight reduction and glycaemic control, but also potentially restoring reproductive hormone balance.
“Results from this study show that there is a direct correlation between the use of anti-obesity medications and testosterone levels,” said Portillo Canales. “Doctors and their patients can now consider this class of medications not only for the treatment of obesity and to control blood sugar, but also to benefit men’s reproductive health.”
Implications for Clinical Practice
The study underscores the broader systemic benefits of GLP-1-based therapies and other anti-obesity agents, particularly in populations at high risk of endocrine dysfunction. By contributing to weight loss and improving metabolic health, these treatments may also serve as valuable tools in addressing hypogonadism in men affected by obesity or type 2 diabetes.
While further research is warranted to confirm causality and examine long-term effects, these findings support a more holistic view of obesity pharmacotherapy — one that encompasses not only cardiometabolic outcomes but also hormonal and reproductive health.
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Sustained weight loss seen even when GLP-1 availability is inconsistent
Key Takeaways:
- Even with inconsistent access to GLP-1 medications, people achieved substantial weight loss when treatment was combined with lifestyle interventions and coaching.
- Participants who experienced gaps in their GLP-1 treatment still saw an average weight loss exceeding 13% after one year.
- Consistent use of GLP-1 medications alongside lifestyle changes produced the most pronounced weight reductions, underscoring the value of an integrated approach.
Research underscores weight loss success despite gaps in GLP-1 treatment
Popular anti-obesity medications continue to deliver meaningful weight loss results, even when access is inconsistent, according to new research presented at ENDO 2025, the Endocrine Society’s annual meeting held in San Francisco, California. The findings were shared by Calibrate, a privately held weight-loss company based in New York.
Kaelen L. Medeiros, M.S., director of data and research at Calibrate, highlighted the difficulties many people face in maintaining uninterrupted treatment. “Patients taking GLP-1 treatments like semaglutide and tirzepatide often face challenges consistently accessing their medications due to supply shortages or insurance coverage obstacles,” she explained.
Impact of treatment interruptions
To explore how such interruptions might affect outcomes, researchers examined data from people enrolled in Calibrate’s commercial metabolic health programme. This programme integrates intensive lifestyle change with medical treatment, focusing on four key areas of metabolic health: food, exercise, sleep, and emotional wellbeing. Participants also benefited from personalised, one-on-one health coaching.
The study analysed records from 6,392 individuals living with overweight or obesity who had received at least one month of GLP-1 treatment and completed a minimum of one year in the programme. Among these, 72.5% experienced at least one disruption in their GLP-1 access, while 11.1% faced multiple disruptions. On average, participants received 8.13 GLP-1 prescriptions in the first year, increasing to 15.25 in the second year.
Weight loss outcomes across groups
Despite the access challenges, participants still achieved notable weight loss. After 12 months:
- Those who experienced interruptions in their medication saw an average weight reduction of 13.7%.
- Those without any treatment gaps achieved an average weight loss of 17%.
At 24 months, the figures rose to:
- 14.9% average weight loss for participants with treatment disruptions.
- 20.1% average weight loss for those with uninterrupted access.
Even participants who received only between one and four GLP-1 treatments over the course of a year achieved clinically meaningful weight reductions, losing over 10% of their body weight on average.
The role of lifestyle change and coaching
“While unpredictable GLP-1 medication access is frustrating, the good news is that our research shows effective weight loss can still be achieved if paired with appropriate lifestyle changes and coaching support,” said Medeiros.
She added, “Given the often-unpredictable availability and shifting insurance coverage associated with anti-obesity medications, it’s important that patients understand the significant impact that lifestyle changes and coaching paired with treatment can have on their health outcomes.”
Consistency remains the most effective approach
While the findings underscore that significant weight loss is possible even when GLP-1 medication use is inconsistent, Medeiros emphasised that a steady, uninterrupted course of treatment combined with comprehensive lifestyle support remains the most effective strategy.
This research provides further reassurance for people managing overweight and obesity that meaningful progress can be made even when medication access is not always predictable, particularly when combined with structured lifestyle interventions and personalised coaching.
CCH Insight:
This study shows that significant weight loss can be achieved despite an interrupted supply of GLP-1 medications, but not as much as with a continuous supply. Although the reporting emphasises the fact that participants received diet and lifestyle coaching, the study cannot make any conclusions regarding its impact, because all participants received the coaching – there was no control group without coaching for comparison. These medicines are meant to be used as an adjunct to diet and lifestyle advice, and outcomes are likely to be better when this is the case, but this study does not provide evidence to support that.
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