Sodium glucose cotransporter 1 (SGLT1) inhibitors in cardiovascular protection: Mechanism progresses and challenges

Pharmacol Res. 2022 Feb:176:106049. doi: 10.1016/j.phrs.2021.106049. Epub 2021 Dec 29.

Abstract

In recent years, multiple clinical trials have shown that sodium glucose cotransporter 1 (SGLT1) inhibitors have significant beneficial cardiovascular effects. This includes reducing the incidence of cardiovascular deaths and heart failure hospitalizations in people with and without diabetes, as well as those with and without generalized heart failure. The exact mechanism responsible for these beneficial effects is not completely understood. To explain the cardiovascular protective effects of SGLT1 inhibitors, several potential arguments have been proposed, including decreasing oxidative stress, regulating cardiac glucose uptake, preventing ischemia/reperfusion injury, alleviating the activation of cardiac fibroblasts, attenuating apoptosis, reducing intermittent high glucose-induced pyroptosis, ameliorating cardiac hypertrophy, attenuating arrhythmic vulnerabilities, and improving left ventricular systolic disorder. This article reviews the advantages and disadvantages of these mechanisms, and attempts to synthesize and prioritize mechanisms related to the reduction of clinical events.

Keywords: Diabetic cardiomyopathy; Heart failure; Ischemia/reperfusion injury; Reactive oxygen species; SGLT1 inhibitor; Sodium glucose cotransporter 1.

Publication types

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

MeSH terms

  • Animals
  • Cardiotonic Agents / pharmacology
  • Cardiotonic Agents / therapeutic use*
  • Cardiovascular Diseases / prevention & control*
  • Humans
  • Sodium-Glucose Transporter 1 / antagonists & inhibitors*

Substances

  • Cardiotonic Agents
  • Sodium-Glucose Transporter 1