Weight regain after stopping GLP-1 drugs averaged 9.69 kg for semaglutide and tirzepatide, review finds
A pooled analysis of eight randomized trials links stopping GLP-1 drugs to weight regain, which the authors say supports treating obesity medication as long-term therapy.
A review that pooled eight randomized trials found that people regain weight after they stop taking GLP-1 medications, and that the amount regained tracks with how much weight they lost while on treatment [1]. Across 2,372 participants, average regain was 9.69 kg for those taking semaglutide or tirzepatide and 2.20 kg for those taking liraglutide [1].
The analysis, a systematic review and meta-analysis published in 2025, searched medical databases including PubMed from inception through February 1, 2024, and kept eight randomized controlled trials with a total of 2,372 participants, all with a body mass index of at least 27 kg/m² [1]. Researchers extracted data on body weight, waist circumference and BMI both on and off treatment [1].
The pooled estimate for liraglutide was 2.20 kg of regain (95% confidence interval 1.69 to 2.70; P < 0.00001) [1]. For semaglutide or tirzepatide grouped together, regain averaged 9.69 kg (95% CI 5.78 to 13.60; P < 0.00001) [1]. Semaglutide is sold as Ozempic, Wegovy and Rybelsus; tirzepatide as Mounjaro and Zepbound.
The confidence interval for the semaglutide and tirzepatide figure is wide, running from about 5.8 kg to about 13.6 kg, so the pooled average of 9.69 kg carries meaningful uncertainty [1]. The review gives one combined figure for the two drugs rather than separate estimates for each, and those separate estimates have not been reported.
The authors also concluded that the proportion of weight regained was proportional to the amount originally lost — people who lost more regained more [1]. They wrote that regain after stopping occurred regardless of lifestyle interventions, and that GLP-1 receptor agonist treatment "should therefore be considered a chronic therapy to prevent weight regain and associated undesirable outcomes related to obesity" [1].
Several details are not reported. The review does not say how quickly the regain happened, whether it leveled off, how long participants were followed after stopping, or what doses they had been taking. It also does not break out results for people with type 2 diabetes versus people treated only for obesity, and it does not report the pooled waist circumference and BMI results. The findings are group averages; individual results varied.
Why it matters for patients
For anyone weighing whether to stop a GLP-1 drug, the practical point is that stopping was not weight-neutral in these trials: participants tended to gain back part of what they had lost [1]. Because the rebound tracked with the original loss, someone who lost a large amount would, on average, be expected to regain more than someone who lost a small amount. The review reports averages across trials and cannot predict what will happen to one person.
The authors' position is that these medicines act like chronic therapies and that stopping removes their effect, which is why they say the possibility of regain "should be discussed when stopping therapy" [1]. What that discussion should include, and what options exist afterward, is not addressed in the review.
Cost, insurance coverage and supply problems — practical reasons many US patients stop — are outside the scope of the analysis and are not addressed [1].
What happens next
The review's evidence cutoff was February 1, 2024, so trials reported after that date are not included [1]. No follow-up study, guideline change or regulatory action tied to this analysis has been announced, and none is disclosed in the review [1].
Sources
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