Post-cessation Weight Regain After Weight Management Medications: A Systematic Review and Meta-Analysis

Area of Science:

• Pharmacology
• Endocrinology
• Obesity Medicine

Background:

• Weight regain after discontinuing pharmacotherapy is a major challenge in obesity management.
• Recent advances include incretin-based medications, necessitating updated analyses of post-cessation weight dynamics.
• Existing syntheses lack focus on studies published since 2020, the era of new pharmacotherapies.

Purpose of the Study:

• To quantify the extent of body weight regain after cessation of approved weight management medications.
• To synthesize evidence from longitudinal studies published from January 2020 onwards.
• To compare weight regain across different classes of weight management drugs.

Main Methods:

• Systematic literature search of PubMed, Embase, Scopus, Web of Science, and Cochrane Library (Jan 2020 - May 2026).
• Inclusion of randomized controlled trials (RCTs) with withdrawal phases, prospective cohort studies, and retrospective database analyses.
• Meta-analysis using a DerSimonian-Laird random-effects model to pool mean percentage body weight regain.

Main Results:

• Seventeen high-quality studies (3 RCTs, 3 prospective cohorts, 11 retrospective analyses; N=3,793) were included.
• Pooled mean weight regain was 7.20% (95% CI: 5.93-8.48).
• Weight regain varied by drug class: Tirzepatide (13.04%), Semaglutide 2.4 mg (7.19%), and Liraglutide 3.0 mg (4.83%).

Conclusions:

• Discontinuation of approved weight management medications consistently results in significant weight regain.
• The magnitude of regain suggests that pharmacotherapy for obesity should be viewed as a chronic disease management strategy.
• Future research should mandate post-cessation follow-up as a primary outcome in clinical trials.