GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis

Randomized controlled clinical trials (RCT) have demonstrated varied efficacy of glucagon-like peptide-1 receptor (GLP-1R) agonists for cardiovascular outcomes. We sought to evaluate the efficacy and safety of GLP-1R agonists among patients with Type 2 diabetes mellitus (DM) for stroke prevention. We conducted a systematic review and meta-analysis of RCTs reporting the following outcomes among patients with Type 2 DM treated with GLP-1R agonists (vs. placebo): nonfatal or fatal strokes, all-cause or cardiovascular mortality, myocardial infarction (MI) and major adverse cardiovascular events (MACE). The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I2 statistics. We identified 8 RCTs, comprising 56,251 patients. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76–0.94, p = 0.002; I2 = 0%) and all strokes (OR 0.84; 95% CI 0.75–0.93, p = 0.001; I2 = 0%) by 16%. Overall, GLP-1R agonists reduced MACE by 13% (OR 0.87; 95% CI 0.81–0.94, p = 0.0003; I2 = 42%), cardiovascular mortality by 12% (OR 0.88; 95% CI 0.81–0.95; p = 0.002; I2 = 0%) and all-cause mortality by 12% (OR 0.88; 95% CI 0.82–0.95, p = 0.0007; I2 = 15%). Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80–0.92; p < 0.0001; I2 = 0%) among patients with prior history of MI or nonfatal strokes. Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Further RCTs are needed to evaluate their role for secondary stroke prevention.