Effects of SGLT2 Inhibitors on Ion Homeostasis and Oxidative Stress associated Mechanisms in Heart Failure

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors present a class of antidiabetic drugs, which inhibit renal glucose reabsorption resulting in the elevation of urinary glucose levels. Within the past years, SGLT2 inhibitors have become increasingly relevant due to their effects beyond glycemic control in patients with type 2 diabetes (T2DM). Although dedicated large trials demonstrated cardioprotective effects of SGLT2 inhibitors, the exact mechanisms responsible for those benefits have not been fully identified. Alterations in Ca²⁺ signaling and oxidative stress accompanied by excessive reactive oxygen species (ROS) production, fibrosis and inflammatory processes form cornerstones of potential molecular targets for SGLT2 inhibitors. This review focused on three hypotheses for SGLT2 inhibitor-mediated cardioprotection: ion homeostasis, oxidative stress and endothelial dysfunction.

Keywords: Endothelial dysfunction; Fibrosis; Heart failure; Inflammation; Ion homeostasis; Oxidative stress; SGLT2 inhibitors.