Biochemical and Pharmacological Mechanisms of GLP-1 and Dual Agonists: Implications for Glycemic Control and Cardiovascular Risk Reduction — A Review

Glucagon-like peptide-1 (GLP-1) receptor agonists and dual incretin agonists, particularly glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor co-agonists, represent a major therapeutic advancement in the management of type 2 diabetes mellitus (T2DM) and obesity. Beyond glycemic control, these agents demonstrate clinically significant benefits in weight reduction, blood pressure modulation, lipid profile improvement, and cardiovascular risk mitigation. This review synthesises biochemical, molecular, and pharmacological mechanisms underlying the clinical effectiveness of GLP-1 receptor agonists and dual agonists such as semaglutide and tirzepatide. Guided by a translational biomedical framework integrating receptor signalling theory and cardiometabolic risk models, this qualitative systematic narrative review evaluates peer-reviewed literature on metabolic pathways, neuroendocrine signalling, inflammatory modulation, and endothelial function. Findings suggest that dual agonists provide additive and potentially synergistic metabolic benefits through complementary receptor activation, enhancing insulin sensitivity, appetite regulation, and vascular protection. The review highlights implications for cardiovascular disease prevention, therapeutic guidelines, and future drug development. Limitations include heterogeneity in clinical trial populations and evolving long-term safety data. Future research should prioritise mechanistic human studies, real-world cardiovascular outcomes, and equity in drug access. Keywords: GLP-1 receptor agonists, dual incretin agonists, tirzepatide, semaglutide, cardiovascular risk, type 2 diabetes, obesity, pharmacology