SGLT2 INHIBITORS: FROM GLYCEMIC CONTROL TO CARDIO-RENAL PROTECTION

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were originally developed as glucose-lowering agents for patients with type 2 diabetes mellitus (T2DM). However, a growing body of robust clinical evidence has demonstrated their profound cardioprotective and nephroprotective effects that extend beyond glycemic control. This review summarizes the current understanding of the mechanisms underlying these benefits and the clinical implications across a wide range of patient populations. We discuss landmark cardiovascular and renal outcome trials, evaluate the physiological and molecular mechanisms, including hemodynamic modulation, anti-inflammatory and antifibrotic effects, and improvements in myocardial and renal energetics, and assess the role of SGLT2 inhibitors in heart failure with reduced and preserved ejection fraction, as well as in chronic kidney disease with and without diabetes. The translation of these findings into clinical guidelines has reshaped therapeutic strategies in both endocrinology and cardiology, underscoring the importance of SGLT2 inhibitors as a cornerstone in cardiorenal protection.