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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@article{fa4f3cac2a104bb4aaa64da004458a7a,
title = "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",
abstract = "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.",
author = "Lauritsen, {Katrine M} and Nielsen, {Bent R R} and Tolbod, {Lars P} and Mogens Johannsen and Jakob Hansen and Hansen, {Troels K} and Henrik Wiggers and Niels M{\o}ller and Gormsen, {Lars C} and Esben S{\o}ndergaard",
note = "{\textcopyright} 2021 by the American Diabetes Association.",
year = "2021",
month = mar,
doi = "10.2337/db20-0921",
language = "English",
volume = "70",
pages = "800--808",
journal = "Diabetes",
issn = "0012-1797",
publisher = "AMER DIABETES ASSOC",
number = "3",

}

RIS

TY - JOUR

T1 - 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

AU - Lauritsen, Katrine M

AU - Nielsen, Bent R R

AU - Tolbod, Lars P

AU - Johannsen, Mogens

AU - Hansen, Jakob

AU - Hansen, Troels K

AU - Wiggers, Henrik

AU - Møller, Niels

AU - Gormsen, Lars C

AU - Søndergaard, Esben

N1 - © 2021 by the American Diabetes Association.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

U2 - 10.2337/db20-0921

DO - 10.2337/db20-0921

M3 - Journal article

C2 - 33334875

VL - 70

SP - 800

EP - 808

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 3

ER -