Cardiovascular Protection by Sodium Glucose Cotransporter 2 Inhibitors: Potential Mechanisms

Am J Med. 2017 Jun;130(6S):S30-S39. doi: 10.1016/j.amjmed.2017.04.009.

Abstract

The mechanism of action of empagliflozin in reducing the risk of adverse cardiovascular outcomes vs placebo in patients with type 2 diabetes mellitus and a high risk of cardiovascular disease in the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial is currently unknown. An antiatherosclerotic effect is considered unlikely given the speed of the observed decrease in cardiovascular mortality. Hemodynamic effects, such as reductions in blood pressure and intravascular volume, and involving osmotic diuresis, may provide a more plausible explanation. Metabolic effects, such as cardiac fuel energetics, and hormonal effects, such as increased glucagon release, may also contribute to the results observed during EMPA-REG OUTCOME. This review discusses the main hypotheses suggested to date.

Keywords: Cardiovascular outcomes; Empagliflozin; Mechanisms; Sodium glucose cotransporter 2 inhibitors.

Publication types

  • Review

MeSH terms

  • Benzhydryl Compounds / therapeutic use*
  • Cardiovascular Diseases / prevention & control*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetic Angiopathies / prevention & control*
  • Diabetic Cardiomyopathies / metabolism
  • Glucosides / therapeutic use*
  • Hemodynamics
  • Hormones / metabolism
  • Humans
  • Hyperglycemia / drug therapy
  • Hyperglycemia / etiology
  • Hypoglycemic Agents / therapeutic use*
  • Sodium-Glucose Transporter 2 Inhibitors*

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Hormones
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin