Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

Int J Mol Sci. 2020 Oct 22;21(21):7833. doi: 10.3390/ijms21217833.


The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

Keywords: SGLT2; cardiovascular disease; chronic kidney disease; diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Autonomic Nervous System Diseases / drug therapy*
  • Autonomic Nervous System Diseases / physiopathology
  • Cardio-Renal Syndrome / drug therapy*
  • Cardio-Renal Syndrome / physiopathology
  • Clinical Trials as Topic
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / physiopathology
  • Glomerular Filtration Rate
  • Hemodynamics / drug effects
  • Humans
  • Ketosis / chemically induced
  • Kidney Glomerulus / physiopathology
  • Sodium-Glucose Transporter 2 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors