Cardiovascular protection in coronary artery disease: mechanistic and clinical insights into SGLT2 inhibitors and GLP-1 receptor agonists

Coronary artery disease (CAD) and its acute manifestation, myocardial infarction (AMI), remain significant global health burdens, with a substantial impact on morbidity and mortality, especially in individuals with Type 2 Diabetes Mellitus (T2DM). The interaction between hyperglycemia, endothelial dysfunction, inflammation, and thrombosis creates a complex pathological environment that contributes to the progression of CAD and its acute complications, including AMI. Over recent years, there has been a shift in the therapeutic approach to CAD, especially in T2DM patients, where pharmacologic agents originally developed for glycemic control have demonstrated notable cardiovascular benefits beyond glucose regulation. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are at the forefront of this paradigm shift. Initially, these agents were designed to improve glycemic control, but their broader cardiovascular protective effects have become increasingly evident, particularly in patients with CAD. This review aims to provide an in-depth exploration of the mechanistic underpinnings of these agents, the clinical data supporting their cardiovascular benefits, and their potential role for patients with CAD.