Physicians' Academy for Cardiovascular Education

SGLT2 inhibitor does not improve cardiac energy metabolism in HF

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial

Literature - Hundertmark MJ, Adler A, Antoniades C, et al. - Circulation. 2023 May 30;147(22):1654-1669. doi: 10.1161/CIRCULATIONAHA.122.062021

Introduction and methods


Although SGLT2 inhibitors have emerged as a cornerstone of treatment for patients with HFrEF or HFpEF [1,2], their precise cardiac mechanism of action remains unclear. Possibly, SGLT2 inhibition improves myocardial energy metabolism [3-7].

Aim of the study

The study aim was to investigate the effects of treatment with empagliflozin on myocardial energetics, serum metabolomics, and cardiorespiratory fitness in HF patients.


The EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) trial was a prospective, single-center, double-blind, placebo-controlled, mechanistic RCT conducted in the UK in which 72 symptomatic patients with nonischemic, chronic HFrEF (LVEF ≤40%; n=36) or HFpEF (LVEF ≥50%; n=36) who received appropriate doses of guideline-directed HF medical therapy were enrolled. Patients were stratified into their respective cohorts (HFrEF vs. HFpEF) and randomized to empagliflozin 10 mg (n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks.


The primary endpoint was change in the cardiac phosphocreatine:ATP (PCr/ATP) ratio from baseline to 12 weeks as measured by magnetic resonance spectroscopy.

Exploratory endpoints included measures of energy metabolism at rest and during dobutamine stress (65% of age-maximum heart rate), myocardial triglyceride content, cardiac function and volumes at rest and during dobutamine stress, measures of cardiac fibrosis, and blood biomarkers related to drug effects on metabolism or neurohormonal activation.

Main results

Primary endpoint

Exploratory endpoints


The EMPA-VISION trial showed that 12-week treatment with empagliflozin did not change cardiac energetics, serum metabolites associated with energy metabolism, LVEF, and cardiorespiratory fitness in patients with HFrEF or HFpEF compared with placebo. The authors conclude that their results do not confirm the “thrifty fuel hypothesis,” which suggests that improved energy provision—by using ketones as substrates—is a central mechanism behind the beneficial clinical effects of SGLT2 inhibition observed in HF patients.


Show references

Find this article online at Circulation.

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