Sodium glucose cotransporter-2 (SGLT2) inhibitors have acquired a central role in the treatment of type 2 diabetes, chronic kidney disease including diabetic kidney disease, and heart failure with reduced ejection fraction. SGLT2 inhibitors lower glucose levels by inducing glycosuria. In addition, SGLT2 inhibitors improve cardiovascular outcomes (3-point MACE), end-stage kidney disease, hospitalization for heart failure, and cardiovascular mortality in people with and without diabetes. The mechanisms underlying these benefits have been extensively investigated, but remain poorly understood. In this review, we first summarize recent trial evidence and subsequently focus on (1) the mechanisms by which SGLT2 inhibitors improve kidney outcomes and (2) the potential role of the kidneys in mediating the cardioprotective effects of SGLT2 inhibitors.
Keywords: Chronic kidney disease; Kidney outcomes; SGLT2 inhibitor; Sodium handling; Tubuloglomerular feedback; Type 2 diabetes.
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.