Inhibition of DPP-4 by alogliptin improves coronary flow reserve and left ventricular systolic function evaluated by phase contrast cine magnetic resonance imaging in patients with type 2 diabetes and coronary artery disease

Int J Cardiol. 2016 Nov 15:223:770-775. doi: 10.1016/j.ijcard.2016.08.306. Epub 2016 Aug 21.

Abstract

Background: The present study determined whether dipeptidyl peptidase-4 (DPP-4) inhibition by alogliptin improves coronary flow reserve (CFR) and left ventricular election fraction (LVEF) in patients with type 2 DM and CAD.

Materials and methods: Twenty patients with type 2 DM and known or suspected CAD were randomly allocated to receive diet therapy plus alogliptin (n=10; mean age, 73.3±6.6y) or a control group given diet therapy and glimepiride (n=10; mean age, 76.7±7.3y). Breath-hold PC cine MR images of the coronary sinus (CS) were acquired using a 1.5T MR scanner and 32 channel cardiac coils to assess blood flow of the CS at rest and during adenosine triphosphate (ATP) infusion. The CFR was calculated as CS blood flow during ATP infusion divided by that at rest. The CFR and LVEF were evaluated by MRI at baseline and at three months after starting therapy.

Results: Hemoglobin A1c (HbA1c) was significantly reduced in both groups (alogliptin, 7.2±0.6% to 6.6±0.5%, p=0.034; control, 6.9±0.4% to 6.4±0.3%, p=0.008). However, CFR and LVEF significantly improved only in the alogliptin group (alogliptin: CFR, 2.15±0.61 to 2.85±0.80, p=0.042; LVEF, 59.4±6.3% to 68.0±8.6%, p=0.03; control: CFR, 2.17±0.37 to 2.38±0.32, p=0.19; LVEF, 58.2±9.1 to 60.3±8.8%, p=0.61). The % increases in CFR and in LVEF positively correlated (R=0.47 by Spearman's correlation coefficient; p=0.036).

Conclusion: The inhibition of DPP-4 by alogliptin improved CFR and LVEF evaluated by MRI in patients with type 2 DM and CAD and the improvement in CFR was associated with increased LV systolic function.

Keywords: Coronary flow reserve; DPP4 inhibitors; Diabetes mellitus; Magnetic resonance imaging.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / epidemiology
  • Diabetes Mellitus, Type 2 / diagnostic imaging
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl Peptidase 4 / physiology
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Fractional Flow Reserve, Myocardial / drug effects*
  • Fractional Flow Reserve, Myocardial / physiology
  • Humans
  • Magnetic Resonance Imaging, Cine / methods*
  • Male
  • Piperidines / pharmacology
  • Piperidines / therapeutic use*
  • Prospective Studies
  • Uracil / analogs & derivatives*
  • Uracil / pharmacology
  • Uracil / therapeutic use
  • Ventricular Function, Left / drug effects*
  • Ventricular Function, Left / physiology

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Piperidines
  • Uracil
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • alogliptin