Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are glucose-lowering drugs used in the treatment of type 2 diabetes (T2D) that have shown additional cardiac and renal benefits. The mechanisms of SGLT2i-mediated cardiorenal protection include blood pressure lowering and endothelial function improvements, enhancement of cardiac and renal hemodynamics, optimization of energetic efficiency through metabolic changes and cellular ion exchanges, reduction of inflammation and oxidative stress with consequent fibrosis reduction, and sympathetic activity modulation. This review explores the most recent data regarding the physiological mechanisms of SGLT2i cardiac and renal benefits, which lie at the root of the solid clinical evidence on cardiorenal protection, making SGLT2i a promising new pharmacological approach to the treatment of patients at high risk of cardiorenal syndrome.
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