Dipeptidyl Peptidase 4 Inhibition Increases Myocardial Glucose Uptake in Nonischemic Cardiomyopathy

BackgroundGlucose 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 ResultsTwelve nondiabetic subjects with nonischemic cardiomyopathy underwent metabolic testing and assessment of myocardial glucose uptake by 18F-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).ConclusionsTherapy with the DPP-4 inhibitor sitagliptin results in increased myocardial glucose uptake in nondiabetic patients with nonischemic cardiomyopathy.