Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression.
This systematic review and nonlinear meta-regression examined how body weight changes after people stop taking GLP-1 receptor agonists (GLP-1RAs), a class of medications widely used for obesity management. Researchers searched five major databases through August 2025 and identified 48 eligible studies. The core quantitative analysis focused on six randomised controlled trials (n = 3,236 participants) and applied a mixed-effects exponential recovery model to characterise the trajectory of weight regain over time. The study found that weight regain after GLP-1RA discontinuation follows a predictable, decelerating pattern: approximately 60% of treatment-related weight loss was regained within one year of stopping. The modelled plateau of regain was estimated at 75.3% (95% CI 68.9–81.6%) of lost weight, suggesting a residual but substantially attenuated long-term benefit. The rate constant of 0.0302 per week corresponded to a regain half-life of roughly 23 weeks. Secondary outcomes (HbA1c, systolic blood pressure) were explored but not the primary focus. Limitations include that most included studies carried moderate risk of bias, weight trajectories beyond 52 weeks were extrapolated rather than directly observed, and heterogeneity across study populations, GLP-1RA agents, and treatment durations may affect generalisability.
Why this grade: The meta-regression is grounded in six RCTs with over 3,000 participants, but the long-term plateau estimate relies on statistical extrapolation beyond observed data, and most constituent studies carried moderate risk of bias, limiting confidence in precise trajectory estimates.
Background Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have emerged as breakthrough agents for weight loss. However, discontinuation is common, and clinical trials have demonstrated significant weight regain following cessation. In this systematic review, we aimed to characterise the trajectory of weight regain after GLP-1RA cessation. Methods This systematic review and meta-regression analysis followed Cochrane and PRISMA guidelines. We searched MEDLINE, Embase, Cochrane Library, Scopus and Web of Science from inception to August 28, 2025 for randomised controlled trials (RCTs), non-randomised interventional studies and observational studies reporting weight outcomes after cessation of GLP-1RAs in adults with overweight or obesity. Weight regain was the primary outcome and was modelled using nonlinear regression. Secondary, exploratory outcomes included HbA1c and systolic blood pressure. The study protocol is registered with PROSPERO (CRD420250631751). Findings A total of 48 relevant studies were included. Weight consistently rebounded after cessation of GLP-1RAs. Six RCTs with 3236 participants were included in the nonlinear meta-regression, which utilised a mixed-effect exponential recovery model with random effects applied to the rate constant. At 1 year post-cessation, 60% of the weight lost during treatment was regained. Beyond 52 weeks, weight trajectories were extrapolated, with weight regain estimated to plateau at 75.3% (95% CI 68.9-81.6) of the weight lost on treatment. The rate constant was 0.0302 per week (95% CI 0.0202-0.0401), corresponding to a half-life of 23.0 weeks (95% CI 17.3-34.3). Most studies were assessed to have a moderate risk of bias. Interpretation GLP-1RA cessation is associated with a predictable and decelerating pattern of weight regain, which appears to plateau below pre-treatment levels, suggesting that partial weight-loss benefit may persist long-term but is substantially attenuated. Funding None.
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