GLP-1 Receptor Agonists and Myocardial Perfusion: Bridging Mechanisms to Clinical Outcomes

Coronary microvascular dysfunction (CMD) is a key contributor to myocardial ischemia and adverse cardiovascular outcomes, particularly in individuals with metabolic disorders such as type 2 diabetes (T2D). While conventional therapies primarily target epicardial coronary disease, effective treatments for CMD remain limited. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as promising agents with cardiovascular benefits extending beyond glycemic control. Preclinical and clinical evidence suggests that GLP-1R activation enhances coronary microvascular function through mechanisms including improved endothelial function, increased nitric oxide bioavailability, attenuation of oxidative stress, and reduced vascular inflammation. Moreover, GLP-1R agonists have been shown to improve myocardial blood flow, myocardial perfusion reserve, and coronary endothelial function, particularly in high-risk populations. Despite these promising findings, inconsistencies remain across studies due to variability in patient populations, study designs, and imaging methodologies. This review summarizes current evidence on the role of GLP-1R agonists in myocardial perfusion, bridging mechanistic insights with clinical outcomes. Further large-scale, well-designed trials are needed to clarify their long-term impact on coronary microcirculation and explore their potential as targeted therapies for CMD.