Meta-analysis confirms weight regain after stopping GLP-1 drugs and easing of gut side effects
A new pooled analysis puts numbers on the regain that follows GLP-1 withdrawal, and reports that stomach and gut side effects generally improve once the drugs are stopped.
A systematic review and meta-analysis in PeerJ has found that adults with overweight or obesity regain weight after they stop taking GLP-1 receptor agonists, and that gastrointestinal side effects generally improve once the drugs are stopped [1][2]. The analysis pooled six studies covering 8,993 patients [1].
The review searched PubMed, Embase, Cochrane Library and Scopus from each database's start through December 2025 and initially retrieved 699 studies [1]. Six studies met the criteria for the pooled analysis: 5,553 patients in a discontinuation group and 3,440 patients who kept taking their medication [1]. The average difference in weight change between the two groups was a mean difference of 17.90 percentage points (95% confidence interval 14.11 to 21.69; P < 0.0001) [1]. Looking within the withdrawal groups only, the average change in body weight from before stopping to after stopping was a mean difference of 9.11 percent (95% CI 7.91 to 10.30; P < 0.0001) [1]. The authors flagged statistical heterogeneity across the included studies (P = 0.0082), meaning the results were not uniform from one study to the next [1].
The included studies covered tirzepatide, semaglutide, liraglutide and dulaglutide, which the review groups together as GLP-1 receptor agonists [1]. In a subgroup analysis, weight regain after stopping tirzepatide was significantly larger than after stopping semaglutide, and the authors suggest that differences in how the drugs work may explain the gap [1]. The abstract does not report the size of that difference for each drug, so the separate figures have not been disclosed.
On side effects, the pooled reports showed that overall adverse reactions decreased after withdrawal, gastrointestinal adverse reactions decreased, and the incidence of cardiovascular events was not affected by stopping the drug [1]. The authors state in their conclusion that a risk of adverse reactions exists while these drugs are being used [1]. Work cited in the same paper notes that high treatment costs and gastrointestinal side effects are among the reasons some patients stop early [2].
Earlier evidence cited in the review gives context for the regain figures. One cited source estimates that about 55% to 65% of the weight lost is regained within a year of stopping [2]. The same paper cites trial data showing average weight reductions of 14.9% with semaglutide 2.4 mg weekly and 20.9% with tirzepatide 15 mg weekly during treatment [2]. The SURMOUNT-4 trial of continued tirzepatide treatment is among the studies referenced [1]. The review's authors declare no competing interests [1], and the paper carries a 2026 copyright line for Qi et al. [1].
Why it matters for patients
The regain pattern is one of the most common questions people raise when they consider stopping a GLP-1 drug, and this analysis adds a pooled estimate to what individual trials have shown. A 9.11 percent average gain within the withdrawal groups, and a 17.90 percentage point gap versus continued treatment, describe group averages. They do not predict what will happen to any single person, and the review reports that results varied between studies [1].
The side-effect findings address another frequent question. Gastrointestinal adverse reactions and overall adverse reactions trended down after the drugs were stopped, which is consistent with what patients often report [1]. The review also found no change in the incidence of cardiovascular events after withdrawal [1], though that reflects the pooled data in these six studies rather than a guarantee for any individual.
What the review does not answer is how people should stop, whether lower maintenance doses or intermittent use change the regain pattern, or how long the regained weight persists. No tapering strategy or restart protocol is evaluated here, and the long-term health effects of regaining weight after treatment are not settled by this analysis. Some follow-up details, including how long patients were tracked in each study, are not broken out in the abstract [1].
The practical takeaway is that regain after stopping is a documented, expected pattern in this body of research rather than a personal failure, and that relief from stomach and gut side effects is also expected. Decisions about stopping, pausing or continuing treatment remain between patients and their clinicians.
Sources
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