CARDIOVASCULAR BENEFITS OF GLP-1 RECEPTOR AGONISTS: EVIDENCE FROM CARDIOVASCULAR OUTCOMES TRIALS (CVOTs)

Cardiovascular disease remains the leading cause of morbidity and mortality among patients with type 2 diabetes mellitus (T2DM). In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as an important therapeutic class capable of providing cardiovascular benefits beyond glycemic control. This review aimed to evaluate the current evidence regarding the cardiovascular effects of GLP-1RAs, with particular emphasis on findings from major cardiovascular outcome trials (CVOTs). A narrative review of randomized controlled trials, meta-analyses, and contemporary clinical guidelines was conducted. Major CVOTs evaluating lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide, oral semaglutide, and efpeglenatide were analyzed with respect to major adverse cardiovascular events (MACE), cardiovascular mortality, stroke, myocardial infarction, heart failure, and renal outcomes. The available evidence demonstrates that several GLP-1RAs significantly reduce cardiovascular risk in patients with T2DM. Liraglutide, semaglutide, dulaglutide, albiglutide, and efpeglenatide consistently showed reductions in MACE, while meta-analyses confirmed favorable effects on cardiovascular mortality, all-cause mortality, and stroke. Additional benefits included improved renal outcomes and clinically meaningful weight loss. Recent evidence from the SELECT trial further suggests that cardiovascular protection may extend to individuals with overweight or obesity without diabetes. In conclusion, GLP-1 receptor agonists have evolved from glucose-lowering agents into therapies with established cardioprotective properties. Their ability to improve cardiovascular outcomes and reduce cardiometabolic risk supports their central role in contemporary diabetes management and cardiovascular prevention strategies.