Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors: JACC State-of-the-Art Review

J Am Coll Cardiol. 2020 Feb 4;75(4):422-434. doi: 10.1016/j.jacc.2019.11.031.

Abstract

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class approved for treatment of diabetes, have been shown to possess a favorable metabolic profile and to significantly reduce atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. Although initially considered to be only glucose-lowering agents, the effects of SGLT2i have expanded far beyond that, and their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes. It is therefore critical for cardiologists, diabetologists, nephrologists, and primary care physicians to be familiar with this drug class. This first part of this 2-part review provides an overview of the current understanding of the mechanisms of the cardio-metabolic-renal benefits of SGLT2i. The second part summarizes the recent clinical trials of SGLT2i.

Keywords: SGLT2 inhibitor; diabetes; heart failure; renal function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cardiovascular System / drug effects
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy
  • Fibrosis
  • Heart / drug effects*
  • Heart Failure / drug therapy
  • Humans
  • Hypertension
  • Hypoglycemic Agents / pharmacology
  • Inflammation
  • Kidney / drug effects*
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Non-alcoholic Fatty Liver Disease / physiopathology
  • Oxidative Stress
  • Renal Insufficiency, Chronic / drug therapy
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / physiopathology

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors