Vascular Effects of Sitagliptin in Diabetes Mellitus

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

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Other: Control; Drug: Sitagliptin; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30625
    • Hannover Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Type 2 Diabetes mellitus

Exclusion Criteria:

• Allergy to sitagliptin
• Treatment with PPAR-gamma agonist

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hannover Medical School
• Investigators: Principal Investigator: Sajoscha A. Sorrentino, M.D., Hannover Medical School

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Anticipated): November 1, 2011
• Study Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: March 26, 2010
• First Submitted That Met QC Criteria: March 30, 2010
• First Posted (Estimate): March 31, 2010

Study Record Updates

• Last Update Posted (Estimate): March 31, 2010
• Last Update Submitted That Met QC Criteria: March 30, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Sitagliptin Phosphate
• Other Study ID Numbers: MHH_NPH_SS_1/2010 (Other Identifier: Hannover Medical School)