Molecular Mechanisms of SGLT2 Inhibitors Bridging Glucose Lowering and Cardiac Protection: A Comprehensive Review

Sodium-glucose cotransporter-2 (SGLT2) inhibitors represent a revolutionary class of antidiabetic medications that have demonstrated remarkable cardiovascular protective effects beyond their primary glucose-lowering action. This comprehensive review examines the intricate molecular mechanisms underlying the dual therapeutic benefits of SGLT2 inhibitors, focusing on their glucose-independent cardioprotective pathways. The review systematically analyzes the molecular targets, signaling cascades, and cellular processes that contribute to improved cardiac outcomes in patients with type 2 diabetes mellitus. Key mechanisms include modulation of cardiac metabolism, reduction in oxidative stress, improvement in endothelial function, anti-inflammatory effects, and direct myocardial protection. The evidence suggests that SGLT2 inhibitors exert their cardioprotective effects through multiple interconnected pathways involving metabolic reprogramming, ion channel modulation, autophagy regulation, and mitochondrial bioenergetics. Understanding these molecular mechanisms is crucial for optimizing therapeutic strategies and developing next-generation cardiovascular protective agents. This review provides a detailed analysis of current evidence supporting the pleiotropic effects of SGLT2 inhibitors and their clinical implications for cardiovascular disease management.