GLP-1 Agonists in Cardiovascular Diseases: Mechanisms, Clinical Evidence, and Emerging Therapies

Glucagon-like peptide-1 (GLP-1) receptor agonists now serve as therapeutic agents for cardiovascular diseases (CVDs) beyond their original use for treating type 2 diabetes mellitus (T2DM). This review combines molecular mechanisms with clinical evidence to demonstrate how GLP-1 agonists help lower cardiovascular risk for conditions, including atherosclerosis, heart failure, stroke, and vascular dementia. These agents produce multiple beneficial effects, which include anti-inflammatory action along with anti-atherogenic effects, endothelial-protective benefits, and cardioprotective actions to minimize major adverse cardiovascular events (MACEs). GLP-1 agonists achieved substantial reductions in myocardial infarction, stroke, cardiovascular mortality, and heart failure events according to major cardiovascular outcome trials (CVOTs). Recent research, notably the pivotal SELECT trial, has confirmed their suitability for non-diabetic subjects with obesity and established CVD. New drug delivery methods and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists demonstrate potent efficacy, with tirzepatide showing significant MACE reduction in its own CVOT. However, significant challenges related to high cost, long-term safety uncertainties, and implementation barriers remain, requiring a balanced perspective. The review presents both mechanistic data and clinical evidence to demonstrate how GLP-1 agonists function as vital cardiovascular medications and outlines future research directions to address critical evidence gaps and maximize their therapeutic effectiveness.