Patients on GLP-1s who stopped taking the drugs maintained about 25% of their weight loss at 1 year, but whether their regained weight is mainly fat or lean mass isn’t clear, new research suggested.

“When we began this work, there was — and still is — a prevailing narrative around GLP-1 receptor agonists (RAs) that says they must be taken indefinitely or ‘you’ll gain it all back, when treatment stops,’” said Brajan Budini and Steven Luo, both medical students at the University of Cambridge, Cambridge, England. “We wanted to assess whether the evidence actually supports that view,” they told Medscape Medical News.

“Specifically, we were curious about whether GLP-1 RAs leave any durable, long-term effects after cessation, and whether they can be incorporated into more balanced strategies, for example, as a temporary phase alongside lifestyle modification,” they said.

Their model projected that weight regain would plateau at a level substantially below baseline, leaving 25% of the original on-treatment weight loss intact. “This challenges the common claim that patients will regain all the weight after stopping treatment and highlights the underlying nuance behind post-cessation weight dynamics,” they said.

The study was published online in eClinical Medicine.

‘Weight Consistently Rebounded’

The researchers conducted a systematic review and meta-regression analysis of the literature from inception to August 29, 2025, of randomized controlled trials (RCTs), non-randomized interventional studies, and observational studies reporting weight outcomes after cessation of GLP-1s in adults with overweight or obesity.

The primary outcome was weight regain, modeled using nonlinear regression. Secondary, exploratory outcomes included A1c levels and systolic blood pressure (SBP).

A total of 48 relevant studies were included in the review, comprising 36 RCTs and 12 non-randomized studies. Treatment durations ranged from 10 to 104 weeks, and post-cessation follow-up durations ranged from 4 to 104 weeks. Most studies were assessed to have a moderate risk for bias.

The researchers found that weight consistently rebounded after cessation of GLP-1s. Using six RCTs, they then conducted a mixed-effects exponential recovery regression to characterize the trajectory of weight regain among 3236 participants (mean age, about 48; about 68% women) with longitudinal data up to 52 weeks after GLP-1 discontinuation. 

At 1 year post-cessation, 60% of the weight lost during treatment had been regained. Secondary outcomes of A1c and SBP generally showed rebound, but the data were insufficient for modeling.

Extrapolating weight trajectories beyond 52 weeks, they found that weight regain was estimated to plateau at 75.3% of the weight lost on treatment.

“GLP-1 RA cessation is associated with a predictable and decelerating pattern of weight regain, which appears to plateau below pretreatment levels, suggesting that partial weight-loss benefit may persist long-term but is substantially attenuated,” the authors concluded.

“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,” Budini and Luo said. “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.”

‘It’s Kind of a Mess’

Commenting on the study for Medscape Medical News, Anne Peters, MD, professor at the Keck School of Medicine of the University of Southern California, said that the findings confirm other studies on weight regain after stopping weight-loss drugs.

Like the authors, she noted, “But the real question is what is the quality of the weight regain and what is the shift in people’s metabolism, and it seems to be very bad,” she said. “Ongoing studies that haven’t been published yet suggest that hypertension comes back. All the inflammatory markers come back, and lipids go up. And if you have diabetes, it gets worse. Overall, it’s kind of a mess.”

Peters pointed to her discussion for Medscape Medical News of a recent BMJ article on weight regain after cessation of different types of weight-management medications (not just GLP-1 RAs) as well as behavioral interventions. That study found that stopping weight-management drugs “is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers.”

Notably, that study also showed that weight was regained faster after the drugs than after behavioral weight-management programs. 

“As these studies and others showed, most people regain the weight,” Peters said. “Whether or not they regain all the weight depends in part on diabetes and insulin and many other factors, but people will likely regain most of their weight.”

“But the message isn’t that you regain the weight. The message is that you may be less healthy when you regain the weight,” she said. “That’s why we need to couple the drugs with lifestyle interventions. And it’s why people who just want to lose 5 or 10 pounds really need to consider that lifestyle change, hard as it is, is the better way to do it.”

The study received no funding. Budini and Luo declared no competing interests.

Marilynn Larkin, MA, is an award-winning medical writer and editor whose work has appeared in numerous publications, including Medscape Medical News and its sister publication MDedge, The Lancet (where she was a contributing editor), and Reuters Health.