SGLT2 Inhibitors in Focus: Redefining Cardiac Safety and Toxicity Mitigation in Cardio-protection and Cardio-Oncology. A Comprehensive Review

Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) have redefined their place in medicine, expanding from diabetes treatment to broader cardiometabolic protection. SGLT2Is, initially developed for type 2 diabetes, have shown robust cardioprotective effects in heart failure with preserved or reduced ejection fraction, as well as in chronic kidney disease. A lot of evidence from trials demonstrates their effectiveness in reducing cardiovascular events, especially hospitalizations for heart failure, in patients with and without diabetes. This has established their role as a fundamental treatment option for heart failure, regardless of ejection fraction. This comprehensive review synthesizes the pharmacologic properties, mechanistic foundations, and clinical evidence supporting the use of SGLT2Is in both conventional cardiovascular disorders and emerging cardio-oncology applications. It clarifies the many ways SGLT2Is protect the heart, particularly in reducing cancer therapy-related cardiac dysfunction (CTRCD). This review also explores the known effects these drugs have on blood flow, metabolism, and heart muscle that contribute to their benefits for the heart and summarizes the growing clinical and preclinical evidence that supports the use of SGLT2Is – especially empagliflozin and dapagliflozin – in the setting of CTRCD. Unique attention is given to recent human trials and translational findings linking SGLT2Is with improved cardiac resilience in cancer survivors. In doing so, this review not only positions SGLT2Is as agents of cardio-protection but also emphasizes the significant change of their integration into modern preventive strategies in cardio-oncology and the wider field of cardiovascular disorders prevention.