GLP-1 Receptor Activation and Cardioprotection: Mechanisms and Clinical Implications

Abstract

Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as important agents with cardiovascular benefits beyond glycemic control. Increasing evidence demonstrates that GLP-1R activation exerts cardioprotective effects through a combination of direct myocardial signaling, vascular modulation, and systemic metabolic improvements. At the cellular level, GLP-1R activation enhances pro-survival pathways, reduces apoptosis, preserves mitochondrial function, and attenuates oxidative stress. Additionally, anti-inflammatory and anti-fibrotic effects contribute to improved cardiac remodeling. Vascular benefits include enhanced endothelial function, nitric oxide–mediated vasodilation, and improved microvascular perfusion. Systemically, GLP-1R agonists improve metabolic parameters such as glucose levels, body weight, and lipid profile, reducing cardiovascular burden. Emerging evidence also highlights GLP-1R–independent mechanisms mediated by peptide metabolites. Together, these mechanisms support the expanding role of GLP-1R agonists in cardiovascular protection, although further research is required to clarify their full therapeutic potential.