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Stopping weight loss drugs linked to weight regain and reversal of heart health markers
Average regain is 0.4kg/month and all weight lost likely to be regained in under 2 years
Weight regain faster after stopping weight loss drugs than after dietary weight loss programmes
Stopping weight loss drugs is followed by weight regain and reversal of beneficial effects on heart and metabolic health markers such as high cholesterol and high blood pressure, finds a study published by The BMJ today.
It shows that the average rate of weight regain is 0.4kg/month after stopping treatment, with weight and risk markers for diabetes and heart disease predicted to return to pre-treatment levels in less than two years.
It also finds that the rate of weight regain after stopping weight loss drugs is almost 4 times faster than after diet and physical activity changes, irrespective of the amount of weight lost during treatment.
“This evidence suggests that despite their success in achieving initial weight loss, these drugs alone may not be sufficient for long term weight control,” say the researchers.
The development of highly effective weight management medications such as glucagon-like peptide-1 (GLP-1) receptor agonists including semaglutide and tirzepatide has transformed the treatment of obesity.
Yet it is estimated that around half of people with obesity discontinue GLP-1 drugs within 12 months, so it’s important to understand what happens to body weight and risk markers for conditions like diabetes and heart disease after stopping treatment.
To do this, a team of researchers from the University of Oxford searched registries and databases for trials and observational studies that compared the effects of any medication licensed for weight loss in adults with any non-drug weight loss intervention (behavioural weight management programmes) or placebo.
The studies were designed differently and varied in quality, but the researchers were able to assess their risk of bias using established tools.
Thirty-seven studies published up to February 2025 involving 9,341 participants were included in the analysis. The average duration of weight loss treatment was 39 weeks, with an average follow-up of 32 weeks.
Participants treated with weight loss drugs regained on average 0.4 kg/month after stopping treatment and were projected to return to their pre-treatment weight by 1.7 years. All cardiometabolic risk markers were projected to return to pre-treatment levels within 1.4 years after stopping the drugs.
Monthly weight regain was also faster after weight loss drugs than after behavioural weight management programmes (by 0.3 kg), independent of initial weight loss.
The authors acknowledge several limitations. For example, only eight studies assessed treatment with the newer GLP-1 drugs and the maximum follow-up period in these studies was 12 months after medication stopped. What’s more, few studies were at low risk of bias.
Nevertheless, they point out that they used three methods of analysis and all provided similar results, adding certainty to their findings.
As such, they conclude: "This evidence cautions against short term use of weight management medications, emphasises the need for further research into cost effective strategies for long term weight control, and reinforces the importance of primary prevention.”
“The study findings casted doubt on the notion that GLP-1 receptor agonists are a perfect cure for obesity,” says a US researcher in a linked editorial.
“People taking GLP-1 receptor agonists should be aware of the high discontinuation rate and the consequences of cessation of medications,” he writes. “Healthy dietary and lifestyle practises should remain the foundation for obesity treatment and management, with medications such as GLP-1 receptor agonists used as adjuncts.”
“Such practises not only help prevent excess weight gain but can also lead to numerous health benefits that go beyond weight control,” he concludes.
Expert Reaction
These comments have been collated by the Science Media Centre to provide a variety of expert perspectives on this issue. Feel free to use these quotes in your stories. Views expressed are the personal opinions of the experts named. They do not represent the views of the SMC or any other organisation unless specifically stated.
Clare Collins is a Laureate Professor in Nutrition and Dietetics at the University of Newcastle and Co-Director of the Food and Nutrition Research Program at the Hunter Medical Research Institute
This systematic review pooled the results from 37 individual studies that had compared the rate of weight regain in adults who had been taking various medication for weight management compared to people in control groups who had either received a lifestyle intervention or no intervention at all.
They had data on over 9,300 adults who had overweight or obesity and found that the rate of weight regain was greater once medication ceased (+400 grams per month) compared to the control groups (+300 grams per month). People had returned to their baseline weight within an average of about 1.7 years after stopping medication.
Interestingly, they also showed that, depending on which medication was used, there was no difference in average body weight between the control groups and medication groups after 1.1 to 1.4 years. This means (what we already knew), that once any intervention ceases, you start to regain weight.
While this is a completely expected result, it was interesting that they also looked at changes in heart and diabetes risk factors as well. Here they estimated that on average people would return to baseline levels of blood cholesterol, triglycerides, glucose, HbA1C [average blood sugar levels] and blood pressure within 1.4 years of ceasing medication.
Where to from here? This highlights that obesity is a chronic relapsing condition with health and medical implications and that these medications will need to be taken long-term (just like other health conditions). More research is needed to identify optimal maintenance medication regimes and what support is needed regarding nutrition, physical activity and psychology to sustain long-term health and wellbeing.
Dr Trevor Steward is Senior Research Fellow in the School of Psychological Sciences at the University of Melbourne
"This meta-analysis confirms what many patients and clinicians have experienced in the real world. Weight loss drugs can help with weight loss while people are on them, but weight often returns after stopping. This is important since many people discontinue because of their high cost, side effects, or the practical burden of ongoing injections. This doesn’t mean these treatments are not valuable. These medicines can contribute to longer-term health benefits, especially when paired with sustainable lifestyle changes. Newer GLP-1 medicines may also differ, and more nuanced research is needed on the latest options, including for people at risk of disordered eating.
The key point is that medications should not be treated as a stand-alone cure. We need better evidence on how these medications work and what to do after stopping, such as how to transition care and what kinds of lifestyle and psychological support help to maintain benefits.
Deciding whether to take a weight management medication should be handled with care. Weight stigma can push people away from the healthcare system and can worsen eating disorders. A fair response should feature equal access, support, and public-health measures that make healthy choices easier, without shame or stigmatising messaging."
Dr Dominika Kwasnicka is a Principal Research Fellow / Associate Professor in Digital Health at The University of Melbourne
"From a behavioural science perspective, this review highlights a key limitation of relying on weight management medications as a stand-alone strategy. The evidence shows that, once these medications are stopped, weight regain occurs relatively quickly and more rapidly than after behavioural weight management programmes. While the projected return to baseline weight and cardiometabolic risk is based on modelling rather than long-term observed data, the underlying pattern is consistent across studies and analyses.
These findings do not suggest that weight management medications are ineffective. On the contrary, they can be highly effective while in use. However, obesity is a chronic condition shaped by behaviours, environments, and ongoing support. Medications primarily act on biological pathways and do not, on their own, establish the behavioural or systemic changes needed to sustain weight loss over time.
For Australia, this has important policy implications. Access to these medications is expanding, often with substantial out-of-pocket costs and limited structured follow-up. Without long-term planning, there is a risk of short-term benefit followed by weight regain and loss of health gains once treatment ceases. These results support the need to embed pharmacotherapy within comprehensive, long-term models of care that include behavioural support, continuity of care, and realistic discussions about duration of treatment, rather than viewing these medications as short-term solutions."
Prof Garron Dodd is the Head of the Metabolic Neuroscience Laboratory at The University of Melbourne and Founder and Chief Scientific Officer of Gallant Bio
“GLP-1 drugs have changed the conversation around obesity and type 2 diabetes, but this new data makes it clear they are a starting point, not a cure. When treatment stops, biology reasserts itself, and weight regain is rapid for many people.
What this study highlight is that obesity is a chronic, relapsing condition. Suppressing appetite pharmacologically works, in part, whilst the drug is present, but it does not reset the underlying neural circuits that regulate hunger, energy balance, and metabolism.
The future of obesity and diabetes treatment will not come from simply making stronger appetite suppressants. It will come from understanding how the brain adapts to weight loss and how we can stabilise those adaptations long-term.
GLP-1 therapies, like Ozempic and Monjario, show us what is possible, but they also expose their limitations. If benefits disappear quickly after stopping treatment, we need to ask deeper questions about durability, resilience, and metabolic memory.
The brain is not just responding to weight loss, it is actively defending body weight. Until we understand and target those central mechanisms, long-term success will remain elusive.
Sustainable treatment will likely require combination approaches, longer-term strategies, and therapies that reshape how the brain interprets energy balance, not just how much people eat.
This study confirms what we are increasingly seeing in clinical practice. When people stop weight-loss medications, weight often returns quickly, and the metabolic benefits fade.
A regain of about 0.4 kilograms a month is concerning but entirely biologically predictable, and it shows why GLP1 medications alone aren’t enough for lasting metabolic health.
Even relatively short periods of weight loss can improve blood sugar control and other health markers, which is encouraging. But we urgently need more research into how those gains can be maintained once treatment stops.
For Australians, this means managing expectations around weight-loss drugs. These medications can be transformative, but they work best as part of ongoing care that prioritises prevention, long-term support, and a deeper understanding of metabolic biology.”
Professor John Dixon is Adjunct Professor in the Iverson Health Innovation Research Institute at Swinburne University of Technology, Melbourne
"This analysis by an excellent UK team shows the data we have all been aware of for years.
The new obesity management medications have greatly improved efficacy, but do not cure the disease of disordered energy balance.
All new medications are expensive initially, and with time and competition, become more cost-effective.
False dichotomies dominate much of the thinking: prevent vs treat, behavioural change vs medical/surgical therapy, and there are so many more.
You can see them emerging in this review."
Joseph Proietto is Professor Emeritus in the School of Medicine at the University of Melbourne
"All those who lose weight medically regain weight. Why? We have 10 hormones in the blood that regulate hunger. When someone loses weight, by the time they lose 5 kg, the levels of these hormones all change to make the individual more hungry (1).
The changes to these hormones is very long-lasting (2). We got evidence all the way to three years (3).
In another change, the reduction in energy expenditure was still in place six years after weight loss, and in that study, they found that leptin, a powerful suppressor of hunger, was still very low (4). This means that the patients must stay on the hunger-suppressing hormones for the rest of their lives."
References:
(1) Edwards KL, et al. Impact of starting BMI and degree of weight loss on changes in appetite-regulating hormones during diet-induced weight loss. Obesity (Silver Spring) 30:911-919 2022
(2) Sumithran P et al. Long term persistence of hormonal adaptations to weight loss N Engl J Med 365;1597 2011
(3) Purcell K. et al. The effect of rate of weight loss on long term weight management: a randomised controlled trial. Lancet Diabetes Endocrinol 2:954-62. 2014
(4) Fothergill E, Guo J, Howard L, et al. Persistent Metabolic adaptation 6 years after “The Biggest Loser” Competition. Obesity 24:1612-1629 2016
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