Dipeptidyl peptidase 4 inhibition increases myocardial glucose uptake in nonischemic cardiomyopathy

J Card Fail. 2012 Oct;18(10):804-9. doi: 10.1016/j.cardfail.2012.07.009.

Abstract

Background: Glucose and fatty acids comprise the primary substrates for myocardial energy metabolism. The normal myocardium switches toward glucose metabolism in the setting of stress; the inability to affect such a switch is a fundamental mechanism behind "diabetic" or "insulin-resistant" cardiomyopathy. The purpose of this mechanistic study was to evaluate the effects of treatment with the dipeptidyl peptidase (DPP) 4 inhibitor sitagliptin on myocardial glucose uptake in patients with nonischemic cardiomyopathy.

Methods and results: Twelve nondiabetic subjects with nonischemic cardiomyopathy underwent metabolic testing and assessment of myocardial glucose uptake by (18)F-fluorodeoxyglucose positron-emission tomographic/computerized tomographic imaging at baseline and after 4 weeks of sitagliptin therapy. Sitagliptin therapy resulted in a significant increase in myocardial glucose uptake (19% increase; P = .04). Although most patients had at least a slight increase in glucose uptake, there was an overall bimodal response, with 6 patients ("responders") demonstrating large increases (>20%) in glucose uptake and 6 patients ("nonresponders") demonstrating <5% increases or slight decreases. Triglyceride-high-density lipoprotein ratios significantly dropped in the 6 responders compared with the 6 nonresponders (P < .02).

Conclusions: Therapy with the DPP-4 inhibitor sitagliptin results in increased myocardial glucose uptake in nondiabetic patients with nonischemic cardiomyopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Cardiomyopathy, Dilated / drug therapy
  • Cardiomyopathy, Dilated / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Fluorodeoxyglucose F18
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Pyrazines / therapeutic use*
  • Sitagliptin Phosphate
  • Statistics as Topic
  • Statistics, Nonparametric
  • Triazoles / therapeutic use*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Pyrazines
  • Triazoles
  • Fluorodeoxyglucose F18
  • Sitagliptin Phosphate