Patients regain weight rapidly after stopping weight loss drugs – but still keep off a quarter of weight lost
It isn’t clear, however, whether the weight regain constitutes both fat and muscle, or mainly fat. Previous studies have suggested that lean body mass – including muscle – can constitute up to 40% of total weight lost during treatment.
More than a billion people worldwide are living with obesity, which increases the risk of diseases such as 2 diabetes, cardiovascular disease and cancer. Weight loss can help mitigate these complications, but losing weight through diet and exercise alone can prove challenging.
In the past few years, a new generation of weight loss drugs has emerged that target a protein known as the glucagon-like peptide 1 receptor (GLP-1R). These drugs help control blood sugar and reduce appetite, and clinical trials have shown they can lead to weight losses of 15 to 20%.
Approximately half of all patients who begin taking these drugs discontinue their use within the first year, however, and three-quarters have stopped after two years. This is likely to be due to their potential side effects and to limited access under insurance coverage policies and national prescribing guidelines.
A team of students at Trinity College, University of Cambridge, has investigated the impact of stopping the medication, modelling the trajectory of weight regain over 12 months and beyond. Their findings are published today in eClinicalMedicine.
The team first carried out a systematic review of existing scientific and medical literature, identifying and summarising all the relevant evidence. They followed this with a meta‑analysis, which pools the results of multiple studies to estimate an overall effect. This approach allowed them to draw more robust conclusions from studies which, on their own, may provide insufficient evidence and sometimes disagree with each other.
In total, the team examined 48 relevant studies, comprising 36 randomised controlled trials (RCTs) and 12 non-randomised studies.
As most of these studies only followed patients for a few weeks after stopping the drugs, the team selected the six RCTs (comprising more than 3,200 individuals in total) that followed patients for up to 52 weeks after discontinuation of the weight loss drugs. They used these to model the trajectory of weight regain, including to extrapolate beyond 52 weeks.
The model estimated that when individuals stopped taking the medication, they underwent rapid initial weight regain, which slowed progressively. By 52 weeks, individuals had regained 60% of their original weight loss.
At 60 weeks, weight regain begins to plateau and is projected to taper off at 75% of the original weight loss. This means that 25% of the initial weight loss may be sustained in the long term. For an individual who had lost a fifth of their weight while on the drugs, this would correspond to a sustained weight reduction of around 5%.
Weight regain trajectories appeared broadly similar for the different types of weight loss drugs targeting GLP-1R.
Brajan Budini, a medical student at the School of Clinical Medicine and Trinity College, University of Cambridge, said: “Drugs such as Ozempic and Wegovy act like brakes on our appetite, making us feel full sooner, which means we eat less and therefore lose weight. When people stop taking them, they are essentially taking their foot off the brake, and this can lead to rapid weight regain.”
The researchers say there are several reasons why people may not return to their original weight even a year after stopping the medications. One reason is that by reducing appetite, these drugs may help individuals develop healthier eating habits, such as reduced portion sizes or more nutritionally-balanced meals, and these habits may persist even after treatment is discontinued. The drugs may also affect the body long-term, altering hormone levels and ‘resetting’ the brain’s appetite control mechanisms.
Steven Luo, also a medical student at the School of Clinical Medicine and Trinity College, said: “When stopping weight loss drugs, doctors and patients should be aware of the potential for weight regain and consider ways to mitigate this risk.
“It’s important that people are given advice on improving their diet and exercise, rather than relying solely on the drugs, as this may help them maintain good habits when they stop taking them.”
There are significant concerns about the long-term consequences of GLP-1R drugs on body composition, with studies indicating that 40 to 60% of the weight lost during treatment is muscle. It was not clear whether individuals regain both fat and muscle.
Budini added: “Our projections show that even though people regain most of the weight they have lost, they still maintain some of the weight loss, but what we currently don’t know is if the same proportion of lean mass is recovered. If the regained weight is disproportionately fat, individuals may ultimately be worse off than before in their fat-to-lean mass ratio, which may have adverse consequences for their health.”
The researchers say there are several limitations to their study. Most importantly, the trial data used to fit their model only extended to 52 weeks after cessation. They also restricted their analysis to studies reporting at least 3kg on-treatment average weight loss.
Reference
Budini, B. & Luo, S. et al. Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression. eClinicalMedicine; 4 Mar 2026; DOI: 10.1016/j.eclinm.2026.103796
A year after stopping taking weight loss drugs such as Ozempic and Wegovy, people regain on average 60% of their lost weight – but beyond this, their weight regain plateaus, with individuals managing to keep off 25% of the weight lost to treatment, say researchers at the University of Cambridge.
Drugs such as Ozempic and Wegovy act like brakes on our appetite. When people stop taking them, they are essentially taking their foot off the brakeBrajan BudiniIuliia BurmistrovaSubcutaneous injection of Semaglutide
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Lack of support for people on weight loss drugs leaves them vulnerable to nutritional deficiencies, say experts
In research published today in Obesity Reviews, the team, led by Dr Marie Spreckley from the University of Cambridge, found a lack of robust evidence surrounding nutritional advice and support and the impact this has on factors such as calorie intake, body composition, protein adequacy, and patient experiences.
Weight loss drugs such as semaglutide and tirzepatide – available under brand names including Ozempic, Wegovy and Mounjaro – mimic the naturally-occurring hormone glucagon like peptide-1 (GLP-1), released into the blood in response to eating. The drugs suppress appetite, increase a feeling of being full, and reduce food cravings.
These drugs can reduce calorie intake by between 16-39%, making them a powerful tool to help people living with obesity and overweight. However, there has been little research to examine their impact on diet quality, protein intake, or adequacy of micronutrients (vitamins and minerals). Evidence suggests that lean body mass – including muscle – can constitute up to 40% of total weight lost during treatment.
Dr Adrian Brown, an NIHR Advanced Fellow from the Centre of Obesity Research at UCL, the study’s corresponding author, said: “Obesity management medications work by suppressing appetite, increasing feelings of fullness, and altering eating behaviours, which often leads people to eat significantly less. This can be highly beneficial for individuals living with obesity, as it supports substantial weight loss and improves health outcomes.
“However, without appropriate nutritional guidance and support from healthcare professionals, there is a real risk that reduced food intake could compromise dietary quality, meaning people may not get enough protein, fibre, vitamins, and minerals essential for maintaining overall health.”
Guidelines from the National Institute for Health and Care Excellence (NICE) recommend semaglutide as an option for weight management for individuals who meet specific criteria, such as a body mass index (BMI) of at least 35.0 kg/m2 and comorbidity (that is, they also have other conditions such as type 2 diabetes, cardiovascular disease, etc). But the guidelines stress that when administered through the NHS, treatment is part of a programme alongside a reduced-calorie diet and increased physical activity in adults.
Most people, however, access the drugs privately. There are currently around 1.5 million people in the UK using GLP-1 drugs, of whom the vast majority – 95% – are thought to access the medication privately, where they are not always provided with the additional nutritional advice and support.
Dr Marie Spreckley, from the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, said: “Use of GLP-1 receptor agonist therapies has increased rapidly in a very short period of time, but the nutritional support available to people using these medications has not kept pace. Many people receive little or no structured guidance on diet quality, protein intake, or micronutrient adequacy while experiencing marked appetite suppression.
“If nutritional care is not integrated alongside treatment, there’s a risk of replacing one set of health problems with another, through preventable nutritional deficiencies and largely avoidable loss of muscle mass. This represents a missed opportunity to support long-term health alongside weight loss.”
Inadequate micronutrient intake can put people at risk of a range of conditions, from fatigue and an impaired immune response to hair loss and osteoporosis. Loss of lean mass – in most cases, muscle – increases the risk of weakness, injury and falls.
The researchers identified just 12 studies that looked at nutrition and diet alongside treatment with semaglutide or tirzepatide. Even then, as the trials varied widely in their approaches to dietary advice and nutritional assessment and lacked standardised protocols and reporting, it was difficult to reach robust conclusions to inform the optimal support for people taking weight loss drugs.
Given the widespread – and increasing – use of these medications and the urgency of providing advice to individuals using the drugs, as well as calling for more research the researchers argue that we can turn to what has been learnt from the guidance and support offered alongside weight loss surgery, such as gastric bands, which leads to similar outcomes to GLP-1 drugs.
Dr Cara Ruggiero, co-author from the MRC Epidemiology Unit at the University of Cambridge, said: “While GLP-1 receptor agonists are increasingly used, there remains a clear gap in structured nutritional guidance. In the interim, we can draw on well-established post-bariatric nutrition principles. Our previous work highlights the importance of prioritising nutrient-dense foods including high-quality protein intake, ideally distributed evenly across meals, to help preserve lean mass during periods of reduced appetite and rapid weight loss.”
While there was insufficient evidence from the studies to recommend strict low-fat diets to complement the weight loss drugs, some observational studies found that people on the treatments often consumed excessive levels of total and saturated fat. This suggests that there might be a need for individualised fat intake guidance, aligned with broad national recommendations, the team says.
Similarly, although meal frequency was not explicitly tested in most trials, they say that strategies such as small, frequent meals may help reduce common side effects such as nausea and improve tolerability, especially in the early stages of treatment.
In calling for more research in this area, the team says it is important that people who use the treatments are consulted to help identify the types of information and wrap-around support that are most meaningful and needed in real-world care. They have launched AMPLIFY (Amplifying Meaningful Perspectives and Lived experiences of Incretin therapy use From diverse communitY voices) to understand how people experience next-generation weight loss therapies when used for weight management.
Dr Spreckley, who is leading AMPLIFY, said: “These medications are transforming obesity care, but we know very little about how they shape people’s daily lives, including changes in appetite, eating patterns, wellbeing, and quality of life. That’s what we’ll explore, working in particular with people from communities historically under-represented in obesity research, to help shape the future of obesity treatment.”
The research was funded by the National Institute for Health and Care Research (NIHR), with additional support from the Medical Research Council and the NIHR UCLH Biomedical Research Centre.
Reference
Spreckly, M et al. Nutrition Strategies for Next-Generation Incretin Therapies: A Systematic Scoping Review of the Current Evidence. Obesity Reviews; 8 Jan 2026; DOI: 10.1111/obr.70079
People prescribed the new generation of weight loss drugs may not receive sufficient nutritional guidance to support safe and sustainable weight loss, leaving them vulnerable to nutritional deficiencies and muscle loss, say experts at UCL and the University of Cambridge.
If nutritional care is not integrated alongside treatment, there’s a risk of replacing one set of health problems with anotherMarie SpreckleyTatsiana Volkava (Getty Images)Close-up of a person administering semaglutide injection for weight loss
The text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright ©University of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.