Cardiovascular and renal benefits of sodium-glucose cotransporter-2 inhibitors: pathophysiologic mechanisms and clinical evidence.

Large-scale clinical outcome trials have demonstrated significant reductions in cardiovascular (CV) and renal outcomes with sodium-glucose cotransporter-2 inhibitors (SGLT2i). These benefits are sustained in patients with a range of left ventricular ejection fractions (LVEF), irrespective of diabetes status, and in a variety of clinical settings, prompting incorporation into clinical practice guidelines for patients with chronic kidney disease (CKD), heart failure (HF), and atherosclerotic cardiovascular disease (ASCVD). The clinical benefits are mediated by an interplay of cardio-metabolic-renal mechanisms, and they have a favorable safety profile. We provide a review of the proposed mechanisms of cardiorenal protection and the evidence supporting the clinical benefits of SGLT2i in CKD, acute and chronic HF treatment and prevention , and ASCVD, highlighting the uses of SGLT2i in clinical practice guidelines.