Effects of SGLT2 Inhibitors beyond Glycemic Control-Focus on Myocardial SGLT1

Int J Mol Sci. 2021 Sep 12;22(18):9852. doi: 10.3390/ijms22189852.

Abstract

Selective sodium-glucose cotransporter 2 (SGLT2) inhibitors reduced the risk of hospitalization for heart failure in patients with or without type 2 diabetes (T2DM) in large-scale clinical trials. The exact mechanism of action is currently unclear. The dual SGLT1/2 inhibitor sotagliflozin not only reduced hospitalization for HF in patients with T2DM, but also lowered the risk of myocardial infarction and stroke, suggesting a possible additional benefit related to SGLT1 inhibition. In fact, several preclinical studies suggest that SGLT1 plays an important role in cardiac pathophysiological processes. In this review, our aim is to establish the clinical significance of myocardial SGLT1 inhibition through reviewing basic research studies in the context of SGLT2 inhibitor trials.

Keywords: SGLT2 inhibitor; dual SGLT1/2 inhibitor; empagliflozin; heart failure; myocardial ischemia; sodium–glucose cotransporter 1; sotagliflozin.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Cardiomyopathies / prevention & control*
  • Heart / drug effects
  • Humans
  • Myocardium / metabolism*
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*
  • Sodium-Glucose Transporter 1 / metabolism
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*

Substances

  • Sodium-Glucose Transporter 1
  • Sodium-Glucose Transporter 2 Inhibitors