| Description: |
Background Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with significant cardiovascular (CV) benefits in patients with type 2 diabetes mellitus (DM). However, the efficacy and safety among different agents across diverse patient populations remain inadequately defined. Purpose We conducted a systematic review, along with pairwise and network meta-analysis, to assess the safety and efficacy of GLP-1 RAs across various patient subgroups and to explore potential variances in outcomes among different GLP-1 RA agents. Methods A systematic search was conducted to identify randomized controlled trials comparing GLP-1 RAs vs placebo or standard care. Primary endpoints comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events (SAEs). Secondary outcomes included myocardial infarction (MI), stroke, heart failure (HF) hospitalization, pancreatitis, infections, gastrointestinal (GI) disorders, and neoplasms. Incident Rate Ratios (IRRs) with 95% confidence intervals (CI) using the random-effects model with inverse variance weighting were calculated. All analyses were run according to a pre-specified subgroup based on the specific GLP-1 RA used. Sensitivity analyses included patients with diabetes mellitus (DM), chronic kidney disease (CKD), obesity or reduced ejection fraction (EF). A Bayesian network meta-analysis including ranking of treatments was performed to explore the comparative effects of different GLP-1 RAs. Results A total of 19 trials encompassing 6967 patient-year and using eight different GLP1-RAs (Lixisenatide, Liraglutide, Exenatide, Semaglutide, Efpeglenatide, Dalaglutide Albiglutide, and Tirzepatide) were included. Mean follow-up duration was 2.2 years. GLP-1 RA reduced all-cause (IRR 0.88, 95% CI 0.83–0.92) and CV (IRR 0.86, 95% CI 0.80–0.92; Figure 1) mortality, MACE (IRR 0.87, 95% CI 0.83–0.91; Figure 2) and SAE (IRR 0.92, 95% CI 0.90–0.94), compared with placebo. GLP-1 RAs reduced MI (-10%), stroke (-10%), ... |