Chronic DPP-4 Inhibition with Sitagliptin Is Associated with Sustained Protection Against Ischemic Left Ventricular Dysfunction in a Pilot Study of Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease
Background—The incretin hormone, glucagon-like peptide-1 (GLP-1), promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous GLP-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4 (DPP-4). We investigated whether chronic DPP-4 inhibition by sitagliptin protected against ischemic left ventricular (LV) dysfunction during dobutamine stress in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).
Methods and Results—19 patients with T2DM underwent dobutamine stress echocardiography (DSE) with tissue Doppler imaging on two separate occasions; the first (control) whilst receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100mg once daily) for approximately four weeks. Sitagliptin increased plasma GLP-1 (7-36) levels and at peak stress, enhanced both global (ejection fraction, 70.5±7.0 versus 65.7±8.0%, p<0.0001; mitral annular systolic velocity, 11.7±2.6 versus 10.9±2.3cm/s, p=0.01), and regional LV function, assessed by peak systolic velocity and strain rate in 12 paired, non-apical segments. This was predominantly due to a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58s-1, p=0.001) whilst no effect was seen in non-ischemic segments (-2.19±0.48 versus -2.18±0.54s-1, p=0.87). At 30 minutes recovery, DPP-4 inhibition mitigated the post-ischemic stunning seen in the control scan.
Conclusions—The addition of DPP-4 inhibitor therapy with sitagliptin to the treatment regime of patients with T2DM and CAD is associated with a sustained improvement in myocardial performance during dobutamine stress, and a reduction in post-ischemic stunning.
Clinical Trial Registration—URL: http://www.isrctn.org. Unique identifier: ISRCTN61646154.
- coronary disease
- glucagon-like peptide-1
- dipeptidyl peptidase-4 inhibitors
- diabetes mellitus
- stress echocardiography
- Received June 11, 2013.
- Accepted January 28, 2014.