Efficacy and Safety of Semaglutide on Cardiovascular Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Cardiovascular complications remain the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM), despite substantial advances in pharmacologic management. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown potential in reducing cardiovascular events through its multifaceted metabolic and anti-inflammatory effects. This systematic review and meta-analysis aimed to assess the efficacy and safety of semaglutide in improving cardiovascular outcomes among patients with T2DM. A comprehensive literature search was conducted across multiple databases up to March 30, 2025. Randomized controlled trials comparing semaglutide with placebo in adults with T2DM were included. Five randomized controlled trials with a total of 19,717 participants were included. Semaglutide was associated with a significant reduction in major adverse cardiovascular events [risk ratios (RR), 0.82; P < 0.00001], cardiovascular death (RR, 0.81; P = 0.05), and need for coronary revascularization (RR, 0.74; P < 0.0001). A significant reduction in cardiac disorder-related adverse events was also observed (RR = 0.80; P = 0.03). No significant difference was noted in all-cause mortality (RR = 0.83; P = 0.16), hospitalization for heart failure (RR = 0.86; P = 0.10) or unstable angina (RR = 0.94; P = 0.63), nonfatal myocardial infarction (RR = 0.82; P = 0.10) or stroke (RR = 0.83; P = 0.06), and vascular disorders (RR = 1.03; P = 0.73). These findings highlight semaglutide's role as a cardioprotective agent, supporting its integration into standard care for high-risk T2DM patients.