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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Tirzepatide outperforms other GLP-1 drugs in diabetes for blood sugar and weight loss
Key Takeaways:
- Tirzepatide demonstrated the strongest reductions in HbA1c and body weight among all GLP-1 RAs analysed, outperforming even Semaglutide and Liraglutide.
- Gastrointestinal side effects were common across long-acting agents, while hypoglycaemia risk varied, with Liraglutide offering a safer profile for some individuals.
- The findings reinforce a clinical shift towards long-acting and dual agonist therapies for managing type 2 diabetes, offering guidance for clinicians, payers, and policymakers.
Growing burden of type 2 diabetes drives search for optimal treatments
Every ten seconds, someone around the globe develops type 2 diabetes mellitus (T2DM) — a chronic disease that substantially raises household healthcare costs and doubles the risk of cardiovascular events such as heart attacks. The worldwide prevalence is projected to soar to 643 million by 2030, intensifying the need for treatments that lower blood glucose levels without contributing to weight gain.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) both stimulate insulin secretion and suppress appetite. However, with a crowded marketplace of differing doses, formulations, and costs, families, clinicians, and health systems continue to seek the medication that offers maximum benefit with minimal drawbacks. This underscores the importance of robust comparative studies.
Rigorous study design to compare eight GLP-1 RAs
In a comprehensive study recently published in Scientific Reports, researchers undertook a systematic review and Bayesian network meta-analysis (NMA) to evaluate the glycaemic, weight, cardiovascular, and safety outcomes of eight GLP-1 RAs. The analysis compared these agents to placebo and standard antidiabetic drugs in adults living with T2DM.
The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA) guidelines and was registered with the International Prospective Register of Systematic Reviews. The research team systematically searched PubMed, Cochrane Library, Embase, Web of Science, and Chinese databases up to 2 October 2024.
Eligible studies were randomised controlled trials (RCTs) lasting at least eight weeks, involving adults with T2DM. These trials compared twice-daily Exenatide (EBID), once-weekly Exenatide (EQW), Semaglutide, Albiglutide, Lixisenatide, Dulaglutide, Liraglutide, or Tirzepatide against each other, placebo, or traditional antidiabetic agents such as insulin, metformin, sodium-dependent glucose transporter 2 (SGLT2) inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas.
For analysis, oral and injectable Semaglutide were grouped due to their comparable efficacy. Independent reviewers conducted study selection, data extraction, and Cochrane risk-of-bias assessments, resolving any differences through consensus.
Outcomes assessed and statistical approach
The primary outcomes were changes from baseline in glycosylated haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG). Secondary outcomes included changes in body weight, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), total cholesterol (TC), high-density and low-density lipoprotein cholesterol (HDL-C, LDL-C), and reported adverse events.
Mean differences (MD) or risk ratios (RR) were calculated with 95% confidence intervals (CIs). When heterogeneity exceeded 50% (as measured by I²), a random-effects model was applied, with Chi-squared tests used to quantify variability.
Tirzepatide shows leading benefits in blood glucose and weight outcomes
From 64 eligible trials involving 25,572 participants, a dense evidence network emerged. Compared with placebo, all GLP-1 RAs lowered HbA1c, but the extent varied markedly:
- Tirzepatide achieved the largest absolute HbA1c reduction (MD −2.3 percentage points; 95% CI −2.7 to −1.9), followed by Semaglutide (−1.5) and Liraglutide (−1.2).
- Lixisenatide’s modest reduction of −0.56 placed it last.
When compared to a pooled group of conventional drugs (including insulin, metformin, SGLT2 inhibitors, DPP-4 inhibitors, and sulfonylureas), only Tirzepatide (−1.5), Semaglutide (−0.73), Liraglutide (−0.40), Dulaglutide (−0.34), and EQW (−0.36) demonstrated statistically significant superiority.
A similar hierarchy was evident for FPG reductions: Tirzepatide lowered FPG by −3.1 mmol/L, followed by Semaglutide (−2.0) and Liraglutide (−1.6). Short-acting agents and Albiglutide offered negligible improvements. The Surface Under the Cumulative Ranking Curve analysis gave Tirzepatide a 100% probability of being the top agent for glycaemic outcomes.
Marked differences in weight outcomes
The weight loss data revealed even starker contrasts. Compared to placebo:
- Tirzepatide achieved a striking −9.1 kg reduction,
- Semaglutide −2.8 kg,
- EBID −1.8 kg, and
- Liraglutide −1.2 kg.
Notably, EBID outperformed Liraglutide in this comparison. When benchmarked against traditional drugs, all GLP-1 RAs except Albiglutide reduced weight, with Dulaglutide and Lixisenatide also showing meaningful effects. Tirzepatide again led with a −10 kg difference.
Changes in blood pressure, BMI, and lipid fractions did not reach statistical significance across interventions, suggesting that glucose and weight benefits did not yet translate into short-term shifts in these cardiovascular parameters.
Safety profile: balancing gastrointestinal effects and hypoglycaemia risk
Gastrointestinal side effects were the most common adverse events. Compared with placebo:
- Semaglutide, Dulaglutide, Liraglutide, Lixisenatide, and Tirzepatide each tripled the risk of nausea and vomiting.
- However, when compared to older drugs already known for gastrointestinal intolerance, the risks were similar.
Hypoglycaemia risk varied considerably:
- EBID and Semaglutide significantly increased episodes (RR 3.3 and 4.6, respectively) versus placebo.
- In contrast, Liraglutide and Lixisenatide actually reduced hypoglycaemia risk compared with traditional regimens, highlighting a possible advantage for people prone to low blood sugar.
Other side effects, such as nasopharyngitis, headache, and elevated lipase levels, showed no material differences. Robust statistical checks (node-splitting, loop inconsistency tests) found no significant discrepancies between direct and indirect comparisons, and funnel plots suggested low publication bias.
Clinical implications and concluding remarks
This analysis positions Tirzepatide as the most effective agent overall for lowering blood glucose and achieving weight loss, with Semaglutide as a reliable second choice. As the authors note, Tirzepatide’s dual agonist activity at GIP and GLP-1 receptors likely underpins its superior outcomes.
Meanwhile, Liraglutide offers moderate glucose improvements with the least risk of hypoglycaemia, potentially making it preferable for leaner adults or those at risk of underweight and frequent hypoglycaemic episodes.
Short-acting formulations and Albiglutide rarely dominated in any category, emphasising the current shift towards once-weekly or dual agonist therapies. Sensitivity and subgroup analyses confirmed these rankings, increasing their practical relevance.
For clinicians, these findings offer valuable guidance in tailoring treatment to individual needs — balancing glucose targets, weight goals, gastrointestinal tolerance, and hypoglycaemia risk. For policymakers and payers, prioritising agents like Tirzepatide or Semaglutide may provide the best outcomes for people with obesity-related diabetes, while reserving Liraglutide for specific patient profiles.
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Global study suggests universal GLP-1 access could halve obesity rates and save millions of lives in five years
Key Takeaways:
- Universal access to GLP-1 receptor agonists could reduce global obesity prevalence by around 52%, potentially improving the health of more than half a billion people.
- A large-scale microsimulation study estimated that such access could prevent approximately 37.5 million deaths over a five-year period by lowering all-cause mortality by nearly 7%.
- Researchers hope these findings will encourage international policy efforts to improve availability and affordability of GLP-1 treatments.
Ambitious modelling seeks to quantify global impact
Universal access to GLP-1 receptor agonists (GLP-1RAs) for eligible people could dramatically cut global obesity rates by half and save tens of millions of lives over just five years, according to new research presented by Elizabeth Staton, a doctoral candidate at Emory University’s Rollins School of Public Health.
“There has been a lot of interest in GLP-1s and how they seem so effective and widely beneficial, but it wasn’t yet quantified what would be that impact on a global level,” Staton told Healio. “We found a probability study … [but] it wasn’t very rigorous.”
Seeking to close this gap, Staton and her team constructed a detailed microsimulation model to predict the worldwide effect of offering GLP-1 therapies such as semaglutide (marketed as Ozempic, Wegovy and Rybelsus by Novo Nordisk) to all eligible individuals. Their work was unveiled during a presentation at a major conference.
The GEM model – a vast global microsimulation
Staton developed what she termed the GEM model (Global Epidemiology Multimorbidity microsimulation model), building on the established Bravo diabetes model created by her colleague Hui Shao, PhD, at the Emory Global Diabetes Research Center.
“I work in a research group in the Emory Global Diabetes Research Center with Hui Shao, PhD, who has a very well-validated Bravo model of diabetes complications. Stemming from that, I’ve created a global epidemiology multimorbidity microsimulation model, which we call the GEM model. This uses peer-reviewed studies for risk ratios, … So then our estimates are slightly more rigorous,” Staton explained.
The study encompassed a synthetic population of roughly 6.57 billion individuals aged 12 years and older, using detailed health data from the 2021 Global Burden of Disease and Non-Communicable Disease Risk Factor Collaboration studies. Eligibility for treatment was defined as having obesity and being at least 12 years old, or having type 2 diabetes with overweight and being at least 18 years old.
“Because it’s a microsimulation, we have individual level data, so we can just subset into people who would fit in the cohort studies. Then we compare our estimates that are predicted vs. the actual cohort studies,” Staton said.
The researchers validated their model by comparing it with prospective cohort studies and existing probability models to ensure robust estimates.
Striking findings on obesity and mortality
The results were remarkable. Staton and colleagues estimated that more than 1 billion people worldwide meet the criteria for semaglutide treatment. Under a scenario of universal access:
- Global obesity prevalence would decline by approximately 52%, an absolute reduction of about 9 percentage points, potentially improving the lives of around 565 million people.
- All-cause mortality would fall by nearly 7%, an absolute reduction of 0.6 percentage points, preventing an estimated 37.5 million deaths within five years.
“The compelling finding is that obesity would be reduced by almost 50% [and] mortality reduced by about 7% globally. These are hugely impactful [estimations] in just a 5-year time horizon,” Staton emphasised.
Hopes for policy and pricing changes
Staton hopes that these findings will help spur global efforts to expand access to GLP-1 therapies. “I hope these data move the conversation about global access forward. There are a number of reasons why access to GLP-1s are limited, with costs, supply and access to providers who prescribe them,” she told Healio.
Ultimately, she hopes that evidence of such a substantial potential benefit might encourage policymakers, manufacturers and global health agencies to invest more heavily in reducing drug costs and expanding prescribing infrastructure.
A tool for thought – not an immediate roadmap
Despite the eye-catching figures, Staton cautioned that this microsimulation is not intended as a direct prediction of what will happen. “The joy of microsimulation is that it’s not really a realistic scenario, but it’s an interesting one to explore,” she said.
Even so, the research underscores the scale of potential benefits if barriers to GLP-1 access could be overcome – offering a powerful data-driven argument for rethinking the global approach to obesity and metabolic disease treatment.
CCH Insight:
The potential benefits of GLP-1 receptor agonists and other, similar, anti-obesity medications are indeed huge, and possibly much greater than predicted in this study, due to the wide-ranging impact of these medicines. Not only do they treat obesity, they also improve glycaemic control and reduce cardiovascular disease risk, and may also protect against liver disease, kidney disease and neurodegenerative diseases like Parkinson’s and dementia.
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Novo Nordisk Expands Digital Health Partnerships to Enhance GLP-1RA Weight Loss Outcomes
Key Takeaways:
- Novo Nordisk launches the Novo Nordisk Partner Platform to integrate digital tools into the care pathway for individuals using semaglutide (Wegovy) for weight loss.
- The initiative seeks collaborations with AI-powered nutrition apps, body composition scanners, telehealth services, and pharmacies to improve clinical outcomes.
- The company aims to consolidate its leadership in the global weight loss market amidst growing competition from Eli Lilly and expanding its obesity pipeline beyond GLP-1 receptor agonists.
Strategic expansion through digital integration
Novo Nordisk has unveiled a new initiative designed to enhance the weight loss outcomes of people receiving treatment with its glucagon-like peptide-1 receptor agonist (GLP-1RA), semaglutide, marketed as Wegovy for obesity and Ozempic for type 2 diabetes. The company is now seeking partnerships with digital health innovators across all stages of the weight management journey to better support individuals in achieving and maintaining clinically significant weight loss.
This effort is being formalised through the Novo Nordisk Partner Platform (NNPP), announced at the HLTH Europe conference in Amsterdam, held from 16 to 19 June. The announcement was made by Anne Cathrine Fleischer, Vice President of Global Obesity Consumer Engagement and New Business Models at Novo Nordisk.
A digital ecosystem for personalised support
Fleischer described the NNPP as a strategy to build a “marketplace of selected solutions” designed to complement pharmacological treatment with digital support. “The idea is that we create this ecosystem or marketplace of selected solutions that people can pick and choose from, so when a patient has started treatment, we know they have received help,” she said.
She continued: “We know when we look at our own digital tools that when intervention is combined with those efficient weight loss medications, patients are receiving better weight loss, so we hope we can significantly improve outcomes by combining education with digital tools.”
Through this platform, individuals prescribed semaglutide for weight management will gain access to additional services such as exercise coaching and nutritional guidance, either via the Novo Nordisk website or its Novo Care platform. The company is also exploring the development of a consolidated mobile application to house these resources in one accessible interface.
Targeting muscle loss and optimising nutrition
A particular focus for the company is addressing muscle mass loss, a known issue associated with GLP-1RA therapies. Novo Nordisk is in discussions with a technology partner whose AI-powered application can scan a person’s plate of food and assess whether it meets their nutritional requirements – especially protein intake.
In addition, the company is exploring collaborations with developers of mobile apps that scan body composition, allowing individuals to monitor changes in lean mass and fat distribution throughout their treatment.
The muscle loss that can accompany GLP-1RA treatment underlines why nutritional expertise matters alongside the medication – the focus of professional training such as the College of Contemporary Health’s Nutrition & Weight Management Essentials, a CPD-accredited online short course.
Broader partnerships to enhance the care pathway
In a bid to offer more integrated care, Novo Nordisk is also seeking partnerships with telehealth providers and community pharmacies to deliver accessible medical advice to people receiving GLP-1RA treatment. “By partnering with these players, we can provide a much better patient journey and care pathway,” Fleischer added.
The company’s approach reflects a broader ambition to deliver not just medication, but a holistic model of obesity care that supports long-term behavioural change and health outcomes.
Advancing the competitive edge in obesity care
Novo Nordisk’s push into digital health partnerships comes as it faces growing competition from Eli Lilly. Earlier this year, Lilly’s dual agonist Zepbound (tirzepatide) demonstrated superior weight loss outcomes to Wegovy in a Phase III clinical trial. Novo Nordisk is responding by accelerating the development of its next-generation therapies.
In early June, the company announced that it had moved both subcutaneous and oral formulations of amycretin into Phase III trials for people living with obesity or overweight. It has also launched two additional Phase III trials of CagriSema, another pipeline candidate.
Further, Novo Nordisk has strengthened its drug discovery capabilities through an $812 million partnership with Deep Apple Therapeutics, aimed at identifying novel small molecules for obesity and other conditions that target pathways beyond GLP-1. This was complemented by a strategic collaboration with NVIDIA, leveraging advanced AI technologies to support future drug development.
With the launch of the NNPP, Novo Nordisk aims to not only optimise outcomes for individuals prescribed GLP-1RAs but also to solidify its leadership in the increasingly competitive obesity treatment landscape by embedding digital innovation across the full spectrum of care.
CCH insight
Industry moves like this reflect a growing consensus that medication works best as part of a wraparound model of obesity care – with nutrition a critical piece. CCH’s Nutrition & Weight Management Essentials CPD short course (10 CPD hours, fully online, CPD-accredited) gives healthcare professionals a solid grounding in nutrition and weight management, including how to help patients on GLP-1 medications meet their protein and micronutrient needs and protect lean muscle during rapid weight loss.
Explore Nutrition & Weight Management Essentials →
Leading health organisations release nutrition guidance for GLP-1 obesity therapies
Key Takeaways:
- Four major U.S. health organisations have released a joint clinical advisory detailing nutrition and lifestyle strategies to support people receiving GLP-1 receptor agonist (GLP-1RA) therapy for obesity.
- The guidance addresses both the therapeutic potential and risks of GLP-1 drugs, such as micronutrient deficiencies, muscle loss, and long-term adherence challenges.
- Eight evidence-based nutritional priorities are outlined, including personalised dietary planning, adequate protein intake, and integrated lifestyle support to improve outcomes and sustain benefits.
Introduction
In an unprecedented collaboration, four prominent American health organisations—the American College of Lifestyle Medicine (ACLM), the American Society for Nutrition (ASN), the Obesity Medicine Association (OMA), and The Obesity Society (TOS)—have released a joint clinical advisory titled “Nutritional Priorities to Support GLP-1 Therapy for Obesity.” Published across four leading peer-reviewed journals, the document presents consensus-driven guidance aimed at equipping clinicians with the tools to support people receiving GLP-1 receptor agonist (GLP-1RA) treatment with comprehensive, evidence-informed nutrition and behaviour strategies.
The Therapeutic Promise and Challenge of GLP-1RAs
GLP-1 therapies—comprising both mono- and combination agents—have become pivotal in modern obesity care. Clinical trials have demonstrated substantial placebo-adjusted weight loss outcomes, ranging from 5% to 18%, alongside significant metabolic, functional, and cardiovascular improvements.
Yet, experts caution that these results cannot be sustained through medication alone. As lead author Dr Dariush Mozaffarian of Tufts University noted:
“GLP-1s represent an important advancement in obesity care. But these medications can present challenges, including gastrointestinal side effects, risk of micronutrient deficiencies, muscle and bone loss, poor long-term adherence with subsequent weight regain, and high costs; and, on their own, are not enough. Nutrition therapy and lifestyle support are essential components to address these challenges, help patients maximise and maintain health gains over time, and ensure we are using these drugs wisely, effectively, and without bankrupting the healthcare system.”
Eight Nutritional Priorities to Support GLP-1 Therapy
The advisory sets out eight core nutritional priorities for clinicians managing people on GLP-1RA therapy:
- Patient-Centred Therapy Initiation – Considering individual goals, preferences, and medical history before prescribing.
- Baseline Nutritional Assessment – Evaluating dietary intake and nutritional status to identify existing deficiencies.
- Gastrointestinal Side Effect Management – Addressing common symptoms such as nausea or constipation that may deter adherence.
- Personalised, Nutrient-Dense Diets – Emphasising minimally processed foods tailored to the individual’s needs.
- Micronutrient Deficiency Prevention – Monitoring and supplementing as necessary to avoid complications.
- Adequate Protein Intake and Strength Training – Preserving lean body mass and preventing sarcopenia.
- Maximising Weight Loss via Diet Quality – Leveraging dietary composition to enhance the efficacy of pharmacotherapy.
- Supporting Broader Lifestyle Change – Integrating physical activity, sleep, mental health, substance use reduction, and social connection.
Evidence for Integrated Care
Several recent studies have reinforced the importance of combined treatment strategies. In research comparing pharmacological treatment alone with integrated care models—including structured nutrition support—people receiving both GLP-1 therapy and nutrition counselling achieved superior weight loss outcomes, greater adherence, and improved weight maintenance post-treatment (Wadden et al., 2021; Kushner et al., 2022).
Despite these promising findings, a significant implementation gap remains. Many individuals prescribed GLP-1RAs do not receive adequate dietary or behavioural guidance, leaving them vulnerable to avoidable adverse outcomes and reduced therapeutic benefit.
Addressing the Care Gap
John E. Courtney, PhD, Chief Executive Officer of the American Society for Nutrition, commented:
“GLP-1s are reshaping the landscape of obesity treatment, but it’s clear that medication alone is not a complete solution. This consensus-based guidance highlights the critical role of nutrition in supporting patients on GLP-1 therapy, with clear recommendations for health care providers to optimise outcomes, reduce risks, and fill urgent gaps in care through practical, evidence-informed nutrition strategies.”
The advisory encourages clinicians to implement a proactive, lifestyle-oriented approach. By prioritising nutrition and behaviour change alongside pharmacotherapy, clinicians can reduce risks such as gastrointestinal intolerance or micronutrient depletion, while enhancing patient outcomes and the cost-effectiveness of care.
A Scalable Strategy Amid a Growing Obesity Crisis
With obesity prevalence continuing to climb globally, the advisory positions integrated nutrition support as a scalable solution for improving the reach and sustainability of GLP-1-based therapies. The authors urge healthcare professionals to consider nutrition therapy and behavioural interventions as integral to every obesity care plan involving GLP-1RAs.
“Clinicians are encouraged to use the advisory’s tools and frameworks to help patients translate nutrition guidance into sustainable behaviours, making lifestyle medicine an active ingredient in every ‘prescription’ for obesity care.”
Publication and Upcoming Discussions
The joint advisory has been published concurrently in the following journals:
- American Journal of Lifestyle Medicine (ACLM)
- The American Journal of Clinical Nutrition (ASN)
- Obesity Pillars® (OMA)
- Obesity (TOS)
Further discussion will take place during the American Society for Nutrition’s annual meeting, NUTRITION 2025, held from 31 May to 3 June in Orlando, Florida:
- Fatima Cody Stanford, MD, will speak on Nutrition Considerations with Long-term Use of GLP-1RA on Saturday, 31 May (07:45–08:15 EDT).
- Monica Agarwal, MD, will present on Nutritional Priorities to Support GLP-1 Therapy for Weight Loss during the Energy and Macronutrient Metabolism (EMM) GEM Forum on Sunday, 1 June (15:05–15:20 EDT).
Conclusion
This advisory marks a critical step toward more holistic, patient-centred obesity care. By embedding evidence-based nutrition and behavioural support within GLP-1 therapy plans, clinicians can better safeguard against side effects, support long-term success, and elevate the standard of care for people living with obesity.
CCH Insight:
These guidelines are very important. They remind us that GLP-1 medications are not just about weight loss, but also about providing lasting health benefits for people living with obesity. This can only really be accomplished by combining the drugs with sustainable changes to diet and lifestyle, and most patients will need help to achieve this. The guidelines also remind us of the potential drawbacks of GLP-1 therapy, like nutrient deficiencies and muscle loss, and the importance of taking steps to minimise the risk of these through an integrated/multidisciplinary approach to obesity care.
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