Cardiovascular and Renal Outcomes of GLP-1 Receptor Agonists in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a foundational therapeutic option for type 2 diabetes mellitus (T2DM), offering glycemic control and cardiovascular benefits. This systematic review and meta-analysis evaluates the impact of GLP-1RAs on cardiovascular outcomes in patients with T2DM. Methods We conducted a comprehensive search of PubMed, Embase, and Cochrane Library up to March 31, 2025, for randomized controlled trials (RCTs) comparing GLP-1RAs with placebo in T2DM patients. Risk ratios (RR) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results Twenty RCTs involving 83,004 patients were included. GLP-1RAs significantly reduced the risk of major adverse cardiovascular events (RR 0.87, 95% CI 0.83–0.92), all-cause death (RR 0.89, 95% CI 0.84–0.93), cardiovascular death (RR 0.88, 95% CI 0.81–0.94), myocardial infarction (RR 0.87, 95% CI 0.79–0.96), stroke (RR 0.88, 95% CI 0.81–0.96) and composite renal outcome (RR 0.80, 95% CI 0.73–0.88) compared to placebo. In addition, a trend of reduction in heart failure hospitalizations (RR 0.93, 95% CI 0.85–1.01), and coronary revascularization (RR = 0.87, 95% CI 0.74 to 1.01) was observed with GLP-1 RAs without reaching statistical significance. Conclusion GLP-1RAs are associated with improved cardiovascular outcomes in patients with T2DM. These findings support current guideline recommendations and highlight their cardioprotective benefits beyond glycemic control in patients with T2DM.