Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 40691794 · doi:10.1186/s12916-025-04200-0
What was done
Authors searched PubMed, Medline, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through March 2024 for randomized controlled trials assessing anti-obesity medications (AOMs) administered for at least 4 weeks with post-discontinuation follow-up of 4 weeks or longer. Weight trajectories after discontinuation were pooled using random-effects meta-analysis and meta-regression.
What was found
- At 4 weeks post-discontinuation: WMD = -0.32 kg (95% CI -3.60 to 2.97, P = 0.85, I² = 83%) versus control. - At 8 weeks post-discontinuation: Significant weight regain versus control (WMD = 1.50 kg, 95% CI 1.32 to 1.68, P < 0.0001, I² = 0.0%). - At 12 weeks post-discontinuation: WMD = 1.76 kg (95% CI 1.29 to 2.24, P < 0.0001, I² = 72.0%). - At 20 weeks post-discontinuation: WMD = 2.50 kg (95% CI 2.27 to 2.73, P < 0.0001, I² = 0.0%). - Subgroup analysis showed significant regain at 12 weeks post-discontinuation only with GLP-1 receptor agonists. Studies with greater on-treatment weight loss or continued lifestyle interventions also demonstrated significant regain.
Why it matters
This review demonstrates that weight rebound begins rapidly within two months of stopping anti-obesity pharmacotherapy, underscoring the chronic nature of obesity management.
Limits
The abstract does not report the total number of included studies or participants. Follow-up is limited to 20 weeks post-discontinuation, and high statistical heterogeneity was present at 4 weeks (I² = 83%) and 12 weeks (I² = 72%). Specific numerical estimates for non-GLP-1 drug classes are not provided in the abstract.
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