title: Chronic dipeptidyl peptidase-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.
abstract: BACKGROUND
  The incretin hormone, glucagon-like peptide-1, promotes myocardial glucose uptake and may improve myocardial tolerance to ischemia. Endogenous glucagon-like peptide-1 (7-36) is augmented by pharmacological inhibition of dipeptidyl peptidase-4. We investigated whether chronic dipeptidyl peptidase-4 inhibition by sitagliptin protected against ischemic left ventricular dysfunction during dobutamine stress in patients with type 2 diabetes mellitus and coronary artery disease.
  
  
  RESULTS
  A total of 19 patients with type 2 diabetes mellitus underwent dobutamine stress echocardiography with tissue Doppler imaging on 2 separate occasions: the first (control) while receiving oral hypoglycemic agents, and the second after the addition of sitagliptin (100 mg once daily) for ≈4 weeks. Sitagliptin increased plasma glucagon-like peptide-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±2.3 cm/s; P=0.01) and regional left ventricular function, assessed by peak systolic velocity and strain rate in 12 paired, nonapical segments. This was predominantly because of a cardioprotective effect on ischemic segments (strain rate in ischemic segments, -2.27±0.65 versus -1.98±0.58 s(-1); P=0.001), whereas no effect was seen in nonischemic segments (-2.19±0.48 versus -2.18±0.54 s(-1); P=0.87). At 30 minutes recovery, dipeptidyl peptidase-4 inhibition mitigated the postischemic stunning seen in the control scan.
  
  
  CONCLUSIONS
  The addition of dipeptidyl peptidase-4 inhibitor therapy with sitagliptin to the treatment regime of patients with type 2 diabetes mellitus and coronary artery disease is associated with a sustained improvement in myocardial performance during dobutamine stress and a reduction in postischemic stunning.
  
  
  BACKGROUND
  URL: http://www.isrctn.org. Unique identifier ISRCTN61646154.
authors: Department of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
authors: Liam M
authors: LM
authors: McCormick
authors: Anna C
authors: AC
authors: Kydd
authors: Philip A
authors: PA
authors: Read
authors: Liam S
authors: LS
authors: Ring
authors: Simon J
authors: SJ
authors: Bond
authors: Stephen P
authors: SP
authors: Hoole
authors: David P
authors: DP
authors: Dutka
mesh_terms: D000368:Aged; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage; D015150:Echocardiography, Doppler; D025401:Echocardiography, Stress / Q000379:methods; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D052216:Glucagon-Like Peptide 1; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy; D010865:Pilot Projects; D011719:Pyrazines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D013318:Stroke Volume / Q000187:drug effects; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: coronary disease; diabetes mellitus; dipeptidyl-peptidase IV inhibitors; echocardiography, stress; glucagon-like peptide-1