Cardiovascular and renal outcomes of GLP-1 receptor agonists in type 2 diabetes mellitus: a systematic review and meta-analysis

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a foundational therapeutic option for type 2 diabetes mellitus (T2DM), offering glycaemic control and cardiovascular benefits. This systematic review and meta-analysis evaluate the impact of GLP-1RAs on cardiovascular outcomes in patients with T2DM.

We conducted a comprehensive search of PubMed, Embase, and Cochrane Library up to 31 March 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. 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.

GLP-1RAs are associated with improved cardiovascular outcomes in patients with T2DM. These findings support current guideline recommendations and highlight their cardioprotective benefits beyond glycaemic control in patients with T2DM.