Effect of empagliflozin on coronary microvascular function in patients with type 2 diabetes mellitus-A randomized, placebo-controlled cross-over study

Hannah Elena Suhrs*, Malin Nilsson, Kira Bang Bové, Mette Zander, Eva Prescott

*Corresponding author for this work


PURPOSE: Results from large scale cardiovascular outcome trials in patients with type 2 diabetes mellitus (DM2) have found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular death and hospitalization for heart failure, but the mechanisms behind the beneficial cardiovascular effects are not fully understood. We tested the hypothesis that the SGLT2i, empagliflozin, improves non-endothelial dependent coronary microvascular function, thereby leading to better cardiac function.

METHODS: Patients with DM2 followed at the endocrinology outpatient clinic at Bispebjerg University Hospital were included in a double blinded, placebo-controlled cross-over study. Participants were allocated equally to each treatment sequence using simple randomization and treated with empagliflozin 25 mg and placebo for 12 weeks, interrupted by 2 weeks wash-out period. The primary outcome was coronary microvascular function, assessed as coronary flow velocity reserve (CFVR) and measured with transthoracic doppler echocardiography. Echocardiographic parameters of cardiac function were measured, and blood samples were analyzed for a broad panel of cardiovascular biomarkers.

RESULTS: Thirteen patients were randomized to each sequence and 10 and 9 completed the study according to protocol, respectively, and were included in the analysis of outcome parameters. We found no improvement in CFVR (change in the empagliflozin period was -0.16 (SD 0.58)). There were no effects on cardiac systolic function or indicators of cardiac filling pressure. Well-known effects of empagliflozin were obtained, such as weight loss and reduction in Hba1c level. Creatinine level increased but remained within normal range. We observed a clear trend of reduction in cardiovascular biomarkers after empagliflozin treatment and increased levels after the placebo period. No serious adverse reactions were reported.

CONCLUSIONS: Despite effect on weight-loss, Hba1c and biomarkers, treatment with empagliflozin for 12 weeks did not improve CFVR in patients with DM2.

Original languageEnglish
Article numbere0263481
JournalPLoS One
Issue number2
Pages (from-to)e0263481
Publication statusPublished - 2022


  • Adult
  • Aged
  • Benzhydryl Compounds/administration & dosage
  • Biomarkers/blood
  • Blood Flow Velocity/drug effects
  • Cardiovascular Diseases/blood
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2/blood
  • Double-Blind Method
  • Echocardiography
  • Echocardiography, Doppler
  • Female
  • Glucosides/administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors/administration & dosage


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