SGLT2 Inhibition Does Not Affect Myocardial Fatty Acid Oxidation or Uptake, But Reduces Myocardial Glucose Uptake and Blood Flow in Individuals With Type 2 Diabetes- a Randomized Double-Blind, Placebo-Controlled Crossover Trial

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Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular morbidity and mortality in individuals with type 2 diabetes. Beneficial effects have been attributed to increased ketogenesis, reduced cardiac fatty acid oxidation and diminished cardiac oxygen consumption. We therefore studied whether SGLT2 inhibition altered cardiac oxidative substrate consumption, efficiency, and perfusion.13 individuals with type 2 diabetes were studied after four weeks treatment with empagliflozin and placebo in a randomized, double-blind, placebo-controlled crossover study. Myocardial palmitate and glucose uptake were measured with 11C-palmitate and 18F-FDG PET/CT. Oxygen consumption and myocardial external efficiency (MEE) were measured with 11C-acetate PET/CT. Resting and adenosine stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) were measured using 15O-H2O PET/CT.Empagliflozin did not affect myocardial FFA uptake but reduced myocardial glucose uptake by 57% (p<0.001). Empagliflozin did not change myocardial oxygen consumption or MEE. Empagliflozin reduced resting MBF by 13% (p<0.01), but did not significantly affect stress MBF or MFR.In conclusion, SGLT2 inhibition did not affect myocardial FFA uptake, but channeled myocardial substrate utilization from glucose towards other sources and reduced resting MBF. However, the observed metabolic and hemodynamic changes were modest and most likely contribute only partially to the cardioprotective effect of SGLT2 inhibition.

Original languageEnglish
JournalDiabetes
Volume70
Issue3
Pages (from-to)800-808
Number of pages9
ISSN0012-1797
DOIs
Publication statusPublished - Mar 2021

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