Vascular Effects of Sitagliptin in Diabetes Mellitus

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid gut hormone secreted in a nutrient-dependent manner that stimulates insulin secretion and inhibits glucagon secretion and gastric emptying, thereby reducing postprandial glycemia.1,2 GLP-1 is derived from posttranslational proteolysis of preproglucagon, and its peptide sequence is identical in mouse, rat, and human.2,3 After secretion from enteroendocrine L cells, GLP-1(7-36) amide is rapidly degraded by dipeptidyl peptidase-4 (DPP-4) to its N-terminally truncated metabolite GLP-1(9-36), which does not interact with the known GLP-1 receptor.4,5 The diverse actions of GLP-1 include the proliferation, differentiation, and protection from apoptosis of pancreatic β cells and the induction of satiety. GLP-1 also improves memory and learning, stimulates afferent sensory nerves, and has neuroprotective functions.1,6 Furthermore, GLP-1 receptor agonists have been reported to have cardiac and vascular actions in rodents and humans that include effects on contractility, blood pressure, cardiac output,7-10 and cardioprotection.11-14

The aim of this study is to evaluate the effect of a therapy with the DPP-4-inhibitor sitagliptin on the prognostic relevant endothelial function and endothelial progenitor cells in patients with type 2 diabetes mellitus.

Primary endpoint: Endothelium-dependent vasodilation before and after treatment of patients with type 2 diabetes mellitus with the DPP-4-inhibitor Sitagliptin and placebo treatment respectively.

Secondary endpoint: effect of sitagliptin on mobilization, NO-production and in vivo regenerative capacity of human endothelial progenitor cells before and after treatment of patients with type 2 diabetes mellitus with the DPP-4-inhibitor sitagliptin and placebo treatment respectively

• Drug: Sitagliptin
  oral tablets 100 mg per day for two weeks
  Other Name: Sitagliptin
• Drug: Placebo
  oral tablet, one per day for two weeks
  Other Name: Placebo
• Other: Control
  no intervention
  Other Name: Control

• Active Comparator: Sitagliptin
  100 mg sitagliptin per day for 2 weeks
  Intervention: Drug: Sitagliptin
• Placebo Comparator: Placebo
  1 placebo tablet per day for 2 weeks
  Intervention: Drug: Placebo
• No Intervention: Healthy Control
  Healthy control subjects
  Intervention: Other: Control

Inclusion Criteria:

• Type 2 Diabetes mellitus

Exclusion Criteria:

• Allergy to sitagliptin
• Treatment with PPAR-gamma agonist