Vascular Effects of Sitagliptin in Diabetes Mellitus

Study Overview
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Brief Summary
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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

Detailed Description
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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

Official Title
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Metabolism-independent Vascular Effects of the Dipetidylpeptidase-4-inhibitor Sitagliptin in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Placebo
* Other: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 Diabetes mellitus Exclusion Criteria: Allergy to sitagliptin Treatment with PPAR-gamma agonist

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sitagliptin<br>100 mg sitagliptin per day for 2 weeks | Drug: Sitagliptin<br>* oral tablets 100 mg per day for two weeks<br>|
| Placebo Comparator: Placebo<br>1 placebo tablet per day for 2 weeks | Drug: Placebo<br>* oral tablet, one per day for two weeks<br>|
| No Intervention: Healthy Control<br>Healthy control subjects | Other: Control<br>* no intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function | Effect of sitagliptin on endothelium-dependent vasodilation before and after treatment of patients with type 2 diabetes mellitus with the DPP-4-inhibitor sitagliptin and placebo treatment respectively | Before and after two week treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on EPCs | 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 | Before and after two week treatment |