NCT02192853

Correlation Between Plasma- and Endothelial DPP-4 Activity

Plasma and Endothelial Activity of Dipeptidyl Peptidase 4 During Different Doses of Sitagliptin

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University Hospital, Gentofte, Copenhagen · Academic / Other
• Sex: All
• Age: 35 Years – 80 Years
• Healthy volunteers: Accepted

Summary

The investigators want to estimate both the endothelial and the plasma activity of dipeptidyl peptidase 4 during different doses of sitagliptin in healthy subjects and patients with type 2 diabetes. Furthermore, the investigators want to investigate whether the current clinical dose of 100 mg of sitagliptin is sufficient to inhibit both the plasma and the endothelial activity of the enzyme dipeptidyl peptidase 4.

Detailed description

The two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from the intestinal L- and K- cells, respectively in response to ingestion of nutrients. The two hormones are able to lower blood glucose levels during high glucose levels - by the so called incretin effect. GIP and GLP-1 are both rapidly inactivated by the enzyme dipeptidyl peptidase 4 (DPP-4). The remaining metabolites are without insulinotropic effects. The effect of DPP-4 inhibitors used in treatment of type 2 diabetes relies on their impact on DPP-4 activity. DPP-4 exists in a soluble form in plasma ad as a membrane-bound form in blood vessels and other tissues. The impact of DPP-4 inhibitors on DPP-4 activity has only been evaluated in plasma. We aim to investigate plasma and endothelial DPP-4 activity (i.e. whole-body DPP-4 activity) in patients with type 2 diabetes during different doses of the DPP-4 inhibitor sitagliptin. Both healthy control subjects and patients with type 2 diabetes are subjected to 4 experimental days (in a randomized order) with continuous infusion of GLP-1 and pre-treatment with 25 mg sitagliptin, 100 mg sitagliptin, 200 mg sitagliptin and placebo, respectively. Afterwards, we are going to measure the whole-body DPP-4 activity by comparing plasma levels of active (intact) GLP-1 and total GLP-1, and relate to plasma DPP-4 activity.

Conditions

• Type 2 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	sitagliptin	In randomized order: Day 1: tablet of 25 mg of sitagliptin + i.v. GLP-1 infusion Day 2: tablet of 100 mg of sitagliptin + i.v. GLP-1 infusion Day 3: tablet of 200 mg of sitagliptin + i.v. GLP-1 infusion
DRUG	Placebo	Day 4: placebo tablet

Timeline

• Start date: 2013-05-01
• Primary completion: 2014-02-01
• Completion: 2014-03-01
• First posted: 2014-07-17
• Last updated: 2017-09-11

Locations

1 site across 1 country: Denmark