Prof Tricia Tan, Professor of Metabolic Medicine, Diabetes and Endocrinology, Imperial College London/Imperial College Healthcare NHS Trust, said:
“This paper highlights the importance of starting weight loss drugs properly, counselling the patients that:
- Obesity and associated metabolic conditions are chronic relapsing conditions
- Treatment needs to be continuous and long term
- Just like when we start BP drugs: patients are aware that this is lifelong, although doses can be adjusted over time depending on the concurrent patient status
- Just like when we start people on treatment for diabetes: this is an indefinite treatment given for benefit.
“However, there is increasing evidence that structured exercise is important to prevent weight regain after cessation of weight loss drugs and this study does not discuss this as a strategy to reduce this problem, instead choosing to dismiss the place of support after cessation of weight loss medications with a single sentence. This is also at odds with their conclusion that weight regain after behavioural weight management programmes is slower than after weight loss medications are stopped.
“Although the paper states that weight regain after weight loss medication is faster than after people undergoing behavioural weight management programmes and perhaps presents this as a problem, behavioural weight management programmes do not in the first instance seem to cause enough weight loss to materially improve cardiovascular disease whereas we do have evidence from weight loss medication treatment that these do improve cardiovascular disease.
“Fundamentally, weight loss medications have been assessed as clinically effective in improving the health of people living with obesity and are cost-effective.
“To ensure that we get maximum value for money for the NHS, the Department of Health should ensure that these treatments are rolled out cohesively and in a long-term plan, ensuring that that there is equity of access across the UK. The current situation, where access is restricted to people who can only afford treatment privately, is clearly inequitable.
“Obesity management, as a whole, must be managed as a national long-term strategy for the benefit of the nation. This should integrate not only GLP-1 drugs but the associated lifestyle therapies and the option of weight loss surgery (which remains our best long-term weight loss treatment).
“Obesity management should be recognised as a powerful contributor to both the long-term health of everyone in the UK as well as returning economic benefits by enabling people to live their best lives.”
Prof John Wilding, Professor of Medicine in the Department of Cardiovascular and Metabolic Medicine & Honorary Consultant Physician, University of Liverpool, said:
“This paper is a comprehensive analysis of the available data on weight regain after cessation of weight loss treatments (note that I am lead author for the STEP 1 extension trial with semaglutide and am also an author for some of the other trials that have addressed this question). I note that quite a lot of the data concerns older medicines that are no longer available, however agree that the data seems to be valid across medication classes and for the newer medicines that are now most commonly used:
“1. The results are not surprising. Obesity is a chronic disease that usually relapses when treatment is stopped. We do not expect interventions for other chronic diseases (e.g. diabetes, high blood pressure or high cholesterol) to continue working when treatment is stopped and there is no scientific reason to expect obesity to be different.
“2. We do know from studies in diabetes and from the SELECT trial of semaglutide in people without diabetes that people at high risk of cardiovascular disease are less likely to have an adverse cardiovascular event such as a heart attack or stroke if they take GLP1 based drugs long term (these studies are usually of 3-5 years duration).
“3. Hence, we should consider these as long-term treatments, not as a quick fix.
“4. I note weight regain tended to be slower after intensive lifestyle interventions. I would be cautious about interpretation of this as the populations included in these trials are likely to be different from those included in trials of medication, and I would always advocate lifestyle support to be used alongside weight loss medications to optimise outcomes anyway.”
Dr Marie Spreckley, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, MRC Epidemiology Unit, University of Cambridge, said:
“This systematic review and meta-analysis brings together 37 studies with 9,341 participants and shows a consistent pattern: after stopping weight management medication, weight is regained and improvements in cardiometabolic risk markers tend to diminish over time. The authors estimate an average weight regain of around 0.4 kg per month after treatment cessation, with weight projected to return to baseline at approximately 1.7 years. In the included trials, weight regain following medication cessation was greater than that observed after behavioural weight management programmes, even when accounting for the amount of weight lost during treatment. The authors also modelled changes in markers such as HbA1c, blood pressure and lipids, projecting a return towards baseline within around 1.4 years after stopping.
“The press release broadly reflects the study’s findings, but it is important to distinguish between observed data and modelled projections. The analysis includes a mix of study designs, and many studies were not at low risk of bias. For newer incretin-based medicines such as semaglutide and tirzepatide, the evidence base remains relatively small and follow-up after stopping treatment is limited to around 12 months. As a result, longer-term statements, including full weight regain within two years, rely on extrapolation beyond the available data. Comparisons with behavioural programmes are indirect and should therefore be interpreted as suggestive rather than definitive.
“In real-world terms, the findings reinforce that obesity management typically requires long-term planning. If people stop medication, many are likely to need ongoing nutritional and behavioural support, and health services should anticipate that cardiometabolic benefits may lessen as weight is regained. The study does not show that behavioural support reliably prevents regain after stopping medication, highlighting the need for further research into effective, scalable strategies for long-term weight maintenance alongside pharmacotherapy.”
Dr Adam Collins, Associate Professor of Nutrition, University of Surrey, said:
“This is a timely and important paper that focuses not on weight loss but on the far greater issue of maintaining any lost weight. Weight recidivism is a common issue seen across all weight loss interventions, and some weight regain in those coming off GLP-1 drugs would be arguably inevitable. Yet, what this paper importantly suggests is that weight regain is amplified when you cease taking these drugs. There are plausible explanations for why. The first relates to how these drugs work. Artificially providing GLP-1 levels several times higher than normal over a long period may cause you to produce less of your own natural GLP-1, and may also make you less sensitive to its effects. No problem when taking the drugs, but as soon as you withdraw this GLP-1 “fix”, appetite is no longer kept in check, and overeating is far more likely. Like any addict, going cold turkey is a real challenge. This is further exacerbated if the individual in question has relied solely on GLP-1 to do the heavy lifting during weight loss, i.e. artificially suppressing their appetite without them establishing any dietary or behavioural changes that would help them in the long run.
“These authors acknowledge that this review is limited by the length of time people have been followed up and by potential bias in these studies. Nevertheless, the authors project, based on the observed studies, that all weight would be regained within 2 years. Yet more worryingly, we know from other weight-loss studies that some people don’t just regain the lost weight but overshoot their original weight. This is particularly concerning given that many people who pay privately for these drugs may not be that overweight to start with.
“So, the key message this paper supports is that weight-loss drugs (GLP-1 agonists) have arguably made weight loss very easy, but maintaining the weight loss is now a bigger challenge than ever. Especially given the massive wave of people who will likely be coming off these drugs in the coming months and years. This emphasises the even greater need for sound diet, behaviour, and lifestyle strategies at both the individual and public health levels.”
Prof Naveed Sattar, Professor of Cardiometabolic Medicine/Honorary Consultant, University of Glasgow, said:
“This is an excellent analysis given the data limitations, but the findings are not unexpected and align with what we already know: weight-loss drugs work well when taken consistently, and weight regain typically occurs after stopping them. It’s also unsurprising that weight loss with medication is somewhat faster than with lifestyle changes, as participants in lifestyle trials tend to be more motivated and have greater self-efficacy compared to those in drug trials.
“Importantly, continued use of these medicines over 3–4 years enables people to maintain significantly lower weight than they would otherwise – a benefit not typically seen with lifestyle-induced weight loss, where many regain weight over time.
“This paper cannot yet tell us whether short-term use offers lasting benefits for organs, but it’s plausible that being lighter for even 2–3 years due to short term use of the medicines could help slow damage to joints or hearts and kidneys. Larger and longer outcome trials will be needed to answer that question.
“Finally, while the editorialist argues that ‘healthy dietary and lifestyle practices should remain the foundation for obesity treatment,’ this overlooks the reality of our highly obesogenic environments. In such settings, medicines are essential for many people living with very high BMIs to manage their weight effectively.”
Declared interests
Prof Tricia Tan: “Previous co-founder, shareholder and consultant for Zihipp Ltd. Not involved since 2024. Scientific Advisory board for Nxera starting Jan 2026.”
Prof John Wilding: “John Wilding reports consultancy / advisory board work for the pharmaceutical industry contracted via the University of Liverpool in the last 36 months (no personal payment) for Alnylam, Amgen, AstraZeneca, Boehringer Ingelheim, Cytoki, Kailera, Lilly, Menarini, Metsera, Napp, Novo Nordisk, Pfizer, Prosciento, Response Pharmaceuticals, Rhythm Pharmaceuticals, Saniona, Shionogi and Ysopia; funding for clinical trials from Amgen, AstraZeneca and Novo Nordisk and personal honoraria / lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Novo Nordisk and Menarini.
“He is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology and the Rank Prize Funds Nutrition Committee. From 2009-2024 he was national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network.”
Dr Marie Spreckley: “I am a registered nutritionist and a researcher in behavioural weight management. I have no financial relationships with industry or manufacturers of GLP-1 or GIP/GLP-1 weight management medications to declare.”
Dr Adam Collins: “I declare no conflict of interest.”
Prof Naveed Sattar: “NS has consulted for and/or received speaker honoraria from Abbott Laboratories, AbbVie, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Janssen, Menarini-Ricerche, Merck Sharp & Dohme, Metsera, Novartis, Novo Nordisk, Pfizer, Sanofi, and Roche; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche. No shares in any medical areas.”
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