Usefulness of Glucagon-Like Peptide-1 Receptor Agonists to Reduce Adverse Cardiovascular Disease Events in Patients with Type 2 Diabetes Mellitus

Evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce cardiovascular disease (CVD) events. The objective of this study was to analyze randomized controlled trials (RCT) testing GLP-1 RA's effect on CVD events among participants with type 2 diabetes (T2DM). RCTs comparing GLP-1 RA versus placebo were identified using the PubMed and Cochrane databases. The endpoints in this study included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi² and I² tests. For any endpoint with significant heterogeneity, a meta-regression was performed using mean baseline hemoglobin A1C (A1C) as the moderator and a R² value was calculated. Seven RCTs (N = 56,004) were identified with 174,163 patient-years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83 to 0.95], cardiovascular death [RR 0.88, 95% CI 0.81 to 0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77 to 0.95]. There was no statistically significant heterogeneity among these RCTs. GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.81 to 1.02]. However, there was significant heterogeneity among these RCTs (Chi² = 12.68, p = 0.05, I² = 53%). When accounting for baseline A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p = 0.23, I² = 27%). A potential linear relationship between baseline A1C and GLP-1 RA's effect on nonfatal MI (R² = 0.64) was observed. In conclusion, GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke; GLP-1 RA did not reduce nonfatal MI, however there may be a linear association between baseline A1C and GLP-1 RA's effect on nonfatal MI.