Abstract 4364905: Beyond Glycemic Control: Cardiovascular Benefits of GLP-1 Receptor Agonists in Type 2 Diabetes

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an essential therapy in type 2 diabetes mellitus (T2DM), providing cardiovascular benefits beyond glycemic control. This meta-analysis evaluated the effects of GLP-1RAs, including oral semaglutide, on major adverse cardiovascular events (MACE) and its key components. Methods: We analyzed nine randomized placebo-controlled cardiovascular outcome trials (CVOTs) enrolling 69,730 patients with T2DM: ELIXA, LEADER, SUSTAIN-6, EXSCEL, HARMONY Outcomes, REWIND, PIONEER 6, AMPLITUDE-O, and SOUL. The primary outcome was MACE, defined as a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Random-effects models were used to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Results: GLP-1RA therapy significantly reduced the risk of MACE by 13% (HR 0.87; 95% CI 0.80–0.93; p < 0.001), cardiovascular death by 12% (HR 0.88; 95% CI 0.80–0.97; p = 0.010), and nonfatal stroke by 15% (HR 0.85; 95% CI 0.78–0.93; p = 0.001). A non-significant 9% reduction was observed for nonfatal myocardial infarction (HR 0.91; 95% CI 0.82–1.01; p = 0.070). Conclusions: GLP-1RAs, including oral semaglutide, confer significant cardiovascular protection in T2DM, notably reducing MACE, cardiovascular death, and nonfatal stroke, with a favorable trend toward lower nonfatal myocardial infarction risk. These findings support GLP-1RAs as a cornerstone strategy for cardiovascular risk reduction in this