Exploring time-varying cardiovascular effects of GLP-1 receptor agonists: A multi-state network meta-analysis of cardiovascular outcome trials
- Design
- Meta-analysis
- Drugs
- Semaglutide
- Assessment
- Not yet reviewed by a person · added Nov 8, 2026
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Abstract
[AIMS] To explore time-varying cardiovascular effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and transition-specific estimates obtainable from published outcome curves. [METHODS] Ten placebo-controlled cardiovascular outcome trials included 87,334 participants and eight GLP-1 RA regimens. Reconstructed major adverse cardiovascular event (MACE) data and all-cause mortality data, directly reconstructed for four trials and synthesised for four, informed a three-state model. Two trials contributed MACE data only. The model assumed no treatment effect on death before a first non-fatal MACE. Conventional random-effects meta-analysis provided a comparator. [RESULTS] Conventional meta-analysis yielded a MACE hazard ratio (HR) of 0.856 (95% confidence interval 0.810-0.905). Modelled transition HRs for first non-fatal MACE at 24 months ranged from 0.51 to 1.38; all 95% credible intervals included 1. Semaglutide posterior median curves suggested larger early reductions that attenuated over time. Mortality attribution depended on structural assumptions, and several sensitivity analyses showed incomplete convergence. [CONCLUSIONS] Conventional synthesis supported a class-level MACE reduction. Multi-state estimates suggested possible time-varying patterns but remained imprecise and assumption-dependent. These data did not establish a reliable efficacy hierarchy or empirically distinguish event prevention from post-event survival effects.