Weight Regain Trajectories After Discontinuation of Semaglutide or Tirzepatide: A Reconstructed Aggregate-Data Bayesian Longitudinal Meta-Analysis
Abstract
Background: Semaglutide and tirzepatide produce substantial weight loss during treatment, but the trajectory of weight regain after discontinuation remains uncertain.
Objective: To estimate post-discontinuation weight-regain trajectories and explore predictors of faster regain.
Methods: We used published timepoint-level aggregate data from studies evaluating weight change after discontinuation of semaglutide or tirzepatide to perform a Bayesian hierarchical longitudinal re-analysis. The model estimated weight loss at cessation, monthly regain rate, time to 50% regain, and time to return to baseline weight. Bayesian meta-regression examined medication type, magnitude of initial weight loss, and post-discontinuation behavioural or lifestyle support. Longer-term estimates assumed a constant linear regain rate.
Results: Six studies comprising 10 intervention arms and 1776 participants were included, with observed follow-up ranging from 4 to 52 weeks. Estimated weight loss at cessation was 15.35 kg (95% credible interval [CrI] 11.18-19.60), followed by regain of 1.04 kg/month (95% CrI 0.80-1.29). Based on the linear model, 50% of initial weight loss was projected to be regained by 7.50 months (95% CrI 5.05-10.57), with return to baseline weight by 15.00 months (95% CrI 10.10-21.13). Tirzepatide showed numerically faster regain than semaglutide in unadjusted analyses, but no clear independent drug-specific difference was evident after adjustment. Greater initial weight loss showed…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,776 participants or records.
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