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Quantification of the Dipeptidyl Peptidase (DPP)-4 Inhibition-mediated Enhancement of the Activity of the Entero-insular Axis

NCT ID: NCT00683735

Last Updated: 2015-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2013-12-31

Brief Summary

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Objective: To assess the effect if co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load). Hypothesis: Treatment with co-administration of sitagliptin and metformin provides a greater incretin effect compared to placebo.

Detailed Description

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A new class of antidiabetic agents, the DPP-4 inhibitors, are thought to protect endogenously secreted incretin hormones (e.g., GLP-1 and GIP) from proteolytic degradation and inactivation. Since GLP-1 has antidiabetogenic properties, an augmentation of meal-related responses of intact, biologically active GLP-1 can be expected to increase the impact of incretin stimulation to insulin secretory responses. The incretin effect in type 2 diabetic patients is reduced due to an impaired secretion of GLP-1 and a reduced insulinotropic effectiveness of GIP. Therefore, sitagliptin (DPP-4 inhibitor) will be studied in 20 type 2-diabetic patients, who will be treated sequentially (crossover design) with (a) placebo, (b) metformin alone, (c) Sitagliptin alone, and (d) a combination of metformin and Sitagliptin for periods of 6 days (with a washout period of 3 days between treatment. The insulin secretory response (insulin, C-peptide, insulin secretion rates determined by deconvolution analysis) will be compared between experiments with oral glucose (75 g) and "isoglycaemic" intravenous glucose infusions (20% glucose i.v.). The difference represents the "incretin effect". It is expected that the incretin effect in type 2-diabetic patients will be enhanced with sitagliptin treatment, especially combined with metformin.

A secondary objective is to relate the potential increase in the % incretin contribution to insulin secretory response after oral glucose (incretin effect) to changes in the oral glucose-induced response of intact GLP-1 and GIP (measured by specific RIAs). Thus, it will be established, to which degree sitagliptin acts as an "incretin enhancer" in type 2 diabetic patients.

This study will also determine how the combination of sitagliptin to metformin affects the incretin response and insulin secretory response. Metformin is a standard and widely used antihyperglycemic agent which lowers glycemic levels primarily through suppression of hepatic glucose output and improvement in peripheral insulin resistance, resulting in increased glucose transport and utilization by skeletal muscle. There are data to suggest that metformin increases endogenous GLP-1 levels in response to an oral glucose load in obese humans (1).

Therefore it is of relevance to confirm this novel activity of metformin in patients with type 2 diabetes, and to assess potential functional consequences regarding the incretin effect.

Conditions

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Diabetes

Keywords

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Incretin, DPP-4, metformin, sitagliptin, insulin secretion

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Treatment A

sitagliptin and placebo

Group Type ACTIVE_COMPARATOR

Sitagliptin

Intervention Type DRUG

100 mg once daily in the morning

Placebo

Intervention Type DRUG

500mg 1-0-0-0

Treatment B

placebo and metformin

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

up to 2000 mg/day

Placebo

Intervention Type DRUG

100mg 1-0-0-0

Treatment C

sitagliptin and metformin

Group Type ACTIVE_COMPARATOR

Sitagliptin

Intervention Type DRUG

100 mg once daily in the morning

Metformin

Intervention Type DRUG

up to 2000 mg/day

Treatment D

placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

500mg 1-0-0-0

Placebo

Intervention Type DRUG

100mg 1-0-0-0

Interventions

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Sitagliptin

100 mg once daily in the morning

Intervention Type DRUG

Metformin

up to 2000 mg/day

Intervention Type DRUG

Placebo

500mg 1-0-0-0

Intervention Type DRUG

Placebo

100mg 1-0-0-0

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Type 2-diabetes mellitus
* BMI 25-35 kg/m2
* HbA1c 6.5%-9% (without OHA medication)
* HbA1c 6%-8.5% (OHA monotherapy with metformin or sulfonylurea)
* Patient understands the study-procedures

Exclusion Criteria

* Type 1-diabetes mellitus
* C-peptide \< 0.7ng/mL (0.23 nmol/L)
* Patient has been taking oral anti-hyperglycemic agent (OHA) within the prior 12 weeks, except metformin or a sulfonylurea
* Patient has required insulin therapy within the past 12 weeks
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Michael A. Nauck

OTHER

Sponsor Role lead

Responsible Party

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Michael A. Nauck

Prof. Dr. med.

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Michael A. Nauck, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Diabeteszentrum Bad Lauterberg

Locations

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Diabeteszentrum Bad Lauterberg

Bad Lauterberg im Harz, , Germany

Site Status

Countries

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Germany

Other Identifiers

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EudraCT: 2008-001663-11

Identifier Type: -

Identifier Source: secondary_id

DZBL 2008-Nauck-01

Identifier Type: -

Identifier Source: org_study_id