March 4, 2026

expert reaction to meta-analysis and modelling study on weight regain after stopping GLP-1 receptor agonists

A meta-analysis published in eClinicalMedicine looks at weight regain trajectories after stopping GLP-1 receptor agonist medication. 

Dr Adam Collins, Associate Professor of Nutrition, University of Surrey, said:

“The paper presents a modern take on an age-old problem: weight regain, or recidivism, after weight loss. It reinforces the findings of the review and meta-analysis earlier this year in the BMJ (West et al) that weight regain is a significant issue after stopping weight loss medication (i.e., GLP-1 RAs). What is novel in this new analysis is the attempt to model the trajectory of weight regain. When viewed this way, the weight regain journey looks the same as that for weight loss, just flipped. In other words, weight change happens quickly at first, then slows and plateaus at a new weight. Based on the studies included, the authors optimistically project that, on average, people regain 60% of their lost weight, but they are likely to retain some weight loss (typically 5% of their original weight), which is clinically meaningful.

“I would say this is an optimistic view of the problem. Typical studies or trials are not always reflective of the real world.  The extent of weight regain varied significantly across the studies included. Those who showed the least regain also incorporated some form of support or intervention after stopping medication, including continuing to take smaller doses of weight loss drugs. This is compounded by the fact that participants in studies are likely to comply with or maintain healthy behaviours simply because they are being monitored (the Hawthorne effect).

“More worryingly, we know from other weight-loss studies that some people not only regain the lost weight but also overshoot their original weight ^[1,2]. I would argue, as I have previously, that coming off GLP-1 RAs and going “cold turkey” may well amplify weight regain, for both physiological and psychological reasons. When we start losing weight, our bodies adapt by conserving energy and restoring lost tissue. The body becomes accustomed to artificially high levels of appetite suppressants and may become less sensitive to their effects or further downregulate the release of its own version. Psychologically, relying solely on the weight loss drugs to do all the work means you may not have addressed any issues with your own diet and lifestyle, which will still be there when you come off the drug.  You cannot presume that just being on the drugs has led the person to establish healthy, sustainable habits that will help them keep the weight off. This makes it critical to have strategies and support in place when “deprescribing” these weight-loss drugs.”

References:

[1] Jacquet et al – https://pmc.ncbi.nlm.nih.gov/articles/PMC7260129/

[2] Pelissier et al – https://pubmed.ncbi.nlm.nih.gov/36645258/

Dr Marie Spreckley, researcher in Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, MRC Epidemiology Unit, University of Cambridge, said:

“This study addresses an important and clinically relevant question: what happens to body weight after stopping GLP-1 receptor agonists. The press release reflects the main findings of the paper. The authors conducted a systematic review of 48 studies and used six large randomised controlled trials with up to 52 weeks of post-cessation follow-up to model percentage weight regain over time. At one year after stopping treatment, around 60% of the weight lost during therapy had been regained, based on pooled trial data.

“It is important to distinguish between observed data and projections. The one-year estimate is supported by empirical follow-up within trials. However, the projection that weight regain will plateau at around 75% of the weight lost is based on extrapolation beyond 52 weeks using a nonlinear exponential recovery model. As with any modelling beyond observed data, uncertainty increases over time, and longer-term follow-up studies are needed to confirm whether this plateau occurs in routine practice.

“These findings are consistent with previous withdrawal trials of semaglutide and tirzepatide, which have shown substantial regain after treatment cessation. Obesity is widely recognised as a chronic, relapsing condition, so it is not unexpected that stopping pharmacotherapy is followed by partial weight regain in many individuals.

“When comparing this study to the BMJ meta-analysis from earlier this year on the same topic by Sam West et al. [1], the difference in emphasis largely reflects modelling choices and outcome metrics. The BMJ paper estimated an average regain of approximately 0.4 kg per month after stopping weight management medications and projected a return to baseline weight at around 1.7 years. That analysis modelled absolute weight change in kilograms, whereas this new paper models percentage of weight regained relative to the weight lost during treatment using a nonlinear exponential approach that assumes rapid early regain followed by progressive slowing. A decelerating trajectory is biologically plausible, but without multi-year empirical data we cannot be certain which projection most closely reflects long term real-world outcomes.

“Key limitations are that only six trials informed the trajectory modelling, most included studies in the broader review were assessed as having moderate risk of bias, and body composition was not incorporated into the model, so it remains unclear whether regained weight represents predominantly fat mass, lean mass, or both. In addition, participants in clinical trials may differ from those treated in routine care.

“Overall, the study reinforces that GLP-1 receptor agonists are unlikely to produce durable weight loss if used as short term interventions without longer term management plans. For many patients, they may need to be considered as part of ongoing treatment strategies alongside nutritional and behavioural support.”

Reference:

[1] https://www.bmj.com/content/392/bmj-2025-085304

‘Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression’ by Brajan Budini et al. was published in eClinicalMedicine at 23:30 UK time Wednesday 4 March 2026.

DOI: 10.1016/j.eclinm.2026.103796

Declared interests

Dr Adam Collins: “I declare no conflict of interest.”

Dr Marie Spreckley: “I am a postdoctoral researcher at the University of Cambridge working on behavioural and nutritional aspects of weight management, including incretin-based therapies. I have not received personal payments from pharmaceutical companies manufacturing GLP-1 receptor agonists.”

For all other experts, no reply to our request for DOIs was received.