Background: Weight management medications, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and newer incretin-based therapies, produce substantial weight loss; however, weight regain following treatment discontinuation remains a major clinical concern. This systematic review and meta-analysis quantified weight regain after cessation of pharmacologic weight management therapy and compared outcomes with continued treatment.

Methods: Seventeen eligible studies, including three randomized controlled trials, three prospective cohort studies, and 11 retrospective studies, were included. A total of 3,793 participants were represented in medication-cessation arms. Pooled estimates of percentage weight regain following discontinuation were calculated, with subgroup analyses performed according to medication type.

Results: The pooled mean weight regain following medication cessation was 7.20% (95% CI: 5.93–8.48), with substantial heterogeneity (I²=97.6%). Medication-specific analyses demonstrated mean weight regain of 7.19% after semaglutide 2.4 mg, 4.83% after liraglutide 3.0 mg, and 13.04% after tirzepatide discontinuation. In randomized controlled trials directly comparing cessation with continued therapy, participants who discontinued medication experienced a 14.26-percentage-point greater weight change (95% CI: 8.86–19.65). Weight regain occurred across medication classes and geographic regions and tended to be greater following discontinuation of therapies associated with larger initial weight reductions.

Conclusion: Discontinuation of weight management medications is associated with clinically significant weight regain, particularly following highly effective incretin-based therapies. These findings reinforce obesity as a chronic, relapsing disease and support consideration of sustained pharmacotherapy when clinically appropriate. Standardized post-discontinuation follow-up and evidence-based maintenance strategies are needed to improve long-term weight management outcomes.

Shivani Shah is a third-year medical student at Caribbean Medical University School of Medicine and is from Toronto, Canada. Throughout medical school, she has been actively involved in medical research, student leadership, community service, and health advocacy. She previously served as a member of the Student Government Association (SGA), contributing to fundraising and charitable initiatives and volunteering to support underserved communities. She is currently volunteering with the American Red Cross Community Preparedness Team and is an active member of the Gender Equity Task Force at the American Medical Women’s Association (AMWA). She has a strong interest in medical research, particularly research inspired by questions encountered during clinical practice. During her Family Medicine and Internal Medicine rotations, she observed the growing use of GLP-1–based medications for weight management, which inspired research examining outcomes after these medications are discontinued. Her work contributed to a systematic review and meta-analysis of 17 longitudinal studies demonstrating clinically significant weight regain following cessation of weight-management medications. The research was subsequently featured by Physician’s Weekly for its clinical relevance. Her interests include medical research, health equity, patient advocacy, and supporting underserved populations.