Glucagon-Like Peptide-1–Based Therapies in Cardiovascular Disease: Evidence, Mechanisms, and Emerging Clinical Applications

Abstract Glucagon-like peptide-1 (GLP-1) receptor agonists were initially developed as glucose-lowering therapies for type 2 diabetes mellitus but have progressively emerged as cardiometabolic agents with clinically relevant cardiovascular effects. Large cardiovascular outcome trials have demonstrated reductions in major adverse cardiovascular events in patients with type 2 diabetes and elevated cardiovascular risk, benefits that extend beyond glycemic control. In parallel, the development of dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonists has further expanded incretin-based therapy by achieving more potent metabolic effects, raising interest in their potential cardiovascular implications. More recently, pharmacologic treatment of obesity with GLP-1–based therapies has been shown to reduce cardiovascular events in patients without diabetes, while emerging evidence supports a role for these agents in selected populations with heart failure with preserved ejection fraction. These effects appear to reflect integrated metabolic, inflammatory, vascular, and hemodynamic mechanisms. This review summarizes current evidence on the cardiovascular effects of GLP-1 receptor agonists and dual GIP–GLP-1 receptor agonists, discusses safety considerations, and highlights future directions for their clinical application across the cardiometabolic continuum.