Rebound or Retention: A Meta-Analysis of Weight Regain After the Discontinuation of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists and Other Anti-obesity Drugs.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials (evaluated with RoB 2.0)
PubMed 41116804 · doi:10.7759/cureus.94926
What was done
A systematic review and meta-analysis of 36 studies published between January 2010 and October 2024 was conducted to quantify weight regain following discontinuation of four anti-obesity medications: semaglutide, liraglutide, exenatide, and orlistat. Databases searched included PubMed, Cochrane Library, Scopus, ScienceDirect, and Web of Science. Risk of bias was evaluated using RoB 2.0, and pooled mean differences (MD) with 95% confidence intervals (CI) were calculated alongside heterogeneity (I²) and publication bias metrics.
What was found
Weight regain occurred across all evaluated agents following treatment cessation. Semaglutide discontinuation resulted in the highest weight regain (MD = -5.15 kg; 95% CI: -5.27 to -5.03), followed by exenatide (MD = -3.06 kg; 95% CI: -3.91 to -2.22), orlistat (MD = -1.66 kg; 95% CI: -2.75 to -0.58), and liraglutide (MD = -1.50 kg; 95% CI: -2.41 to -0.26). Heterogeneity ranged from moderate to very high (I² = 41.7% to 99.7%). Egger's test showed significant publication bias for liraglutide (p = 0.013), with no major bias found for the other drugs.
Why it matters
This review quantifies the extent of weight rebound following the cessation of GLP-1 receptor agonists and orlistat, demonstrating that regain is drug-dependent and largest with more potent agents like semaglutide. It supports the paradigm that obesity requires sustained, long-term therapeutic strategies.
Limits
Heterogeneity was extremely high across studies (I² up to 99.7%), and significant publication bias was detected for liraglutide. The abstract does not report the total participant sample size, baseline patient characteristics, or the post-discontinuation follow-up duration. Some data required extraction via graphical digitization software.
Cited by
- supports Studies show that newer GLP-1 receptor agonists like semaglutide cause more rapid and excessive weight regain after discontinuation compared to older agents like liraglutide and exenatide.