Randomized Controlled Trial of the Hemodynamic Effects of Empagliflozin in Patients With Type 2 Diabetes at High Cardiovascular Risk: The SIMPLE Trial

Diabetes. 2022 Apr 1;71(4):812-820. doi: 10.2337/db21-0721.

Abstract

Treatment with the sodium-glucose cotransporter 2 inhibitor (SGLT-2i) empagliflozin significantly reduces cardiovascular events in patients with type 2 diabetes (T2D); however, the mechanisms behind the reduction in cardiovascular (CV) events are unknown. We investigated whether SGLT-2i treatment affected central hemodynamics during rest and exercise in 34 patients with diabetes in this investigator-initiated, randomized, placebo-controlled, double-blinded trial. The primary end point was change in pulmonary capillary wedge pressure (PCWP) at a submaximal ergometer workload (25 W) after 13 weeks of SGLT-2i treatment (25 mg once daily) compared with placebo. Secondary end points included changes in resting hemodynamics. Baseline and follow-up hemodynamic assessments were performed at rest, submaximal exercise (25 W), and peak exercise using right heart catheterization. Treatment with empagliflozin for 13 weeks in patients with T2D at high CV risk did not reduce left heart filling pressure more than placebo at submaximal exercise. At rest, we observed that empagliflozin reduced PCWP at a magnitude of clinical significance.

Trial registration: ClinicalTrials.gov NCT03151343.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / therapeutic use
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / chemically induced
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucosides
  • Heart Disease Risk Factors
  • Hemodynamics
  • Humans
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Benzhydryl Compounds
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT03151343
  • EudraCT/2016-003743-10