Patients regain 60% of weight lost on GLP-1 drugs within a year of stopping

Credit: Getty Images/Ahmet Yarali

By Olivia Bowthorpe

Patients regain 60% of weight lost on GLP-1 receptor agonist drugs within a year of stopping treatment, according to a systematic review by researchers at the University of Cambridge.

They warned that if the regained weight is predominantly fat, patients could end up with a worse body composition than before starting treatment.

The team analysed 48 published studies, including six randomised controlled trials involving 3,236 participants, to model weight trajectories after stopping drugs such as semaglutide (sold as Wegovy and Ozempic).

Their findings, published in eClinicalMedicine, show rapid initial weight regain that progressively slows. By 52 weeks after cessation, patients had regained 60% of their original weight loss. Projections beyond one year suggest weight regain continues but at a slower rate, eventually plateauing at approximately 75% of the original weight loss.

The study was led by Brajan Budini, a Cambridge medical student, who used trial data and statistical modelling to track how body weight changes after stopping GLP-1RAs. Patterns of weight regain were broadly similar across different types of GLP-1RAs.

"GLP-1 RA cessation is associated with a predictable, decelerating pattern of weight regain, suggesting that partial weight-loss benefit may persist long-term but is substantially attenuated," the authors write.

Concerns over body composition

Beyond weight regain, the researchers highlight significant concerns about long-term effects on body composition. Studies indicate that 40–60% of weight lost during treatment is lean mass, with newer agents such as semaglutide and tirzepatide being less effective in preserving muscle.

"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," said Budini.

"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 call for future trials to investigate the effect of GLP-1 RAs on body composition during and after treatment cessation, and how these changes compare to other weight loss methods.

Implications for prescribing

Approximately half of patients discontinue treatment within the first year, often due to gastrointestinal side effects or financial constraints. However, public health bodies have yet to provide clear guidance on the use of GLP-1 RAs in long-term weight management.

NICE recommends that semaglutide for weight management should be prescribed for a maximum of two years within specialist weight management services. The Cambridge researchers suggest this highlights "a blind spot in long-term obesity management, as the benefits of GLP-1 RAs risk being negated by subsequent weight regain".

They call for a "flexible, individualised approach", noting that appetite suppression caused by these drugs may help patients adopt healthier eating behaviours that persist after treatment stops, though long-term outcomes for weight maintenance and body composition remain uncertain.

Reference: eClinicalMedicine DOI: 10.1016/j.eclinm.2026.103796

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