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Sponsored by: |
Diabeteszentrum Bad Lauterberg im Harz |
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Information provided by: | Diabeteszentrum Bad Lauterberg im Harz |
ClinicalTrials.gov Identifier: | NCT00683735 |
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.
Condition | Intervention | Phase |
---|---|---|
Diabetes |
Drug: Sitagliptin Drug: Metformin Drug: Placebo |
Phase II Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Crossover Assignment, Efficacy Study |
Official Title: | Quantification of the DPP-4 Inhibitin-Mediated Enhancement of the Activity of the Entero-Insular Axis |
Estimated Enrollment: | 20 |
Study Start Date: | June 2008 |
Estimated Study Completion Date: | December 2009 |
Estimated Primary Completion Date: | June 2009 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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Treatment A: Active Comparator
sitagliptin and placebo
|
Drug: Sitagliptin
100 mg once daily in the morning
Drug: Placebo
500mg 1-0-0-0
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Treatment B: Active Comparator
placebo and metformin
|
Drug: Metformin
up to 2000 mg/day
Drug: Placebo
100mg 1-0-0-0
|
Treatment C: Active Comparator
sitagliptin and metformin
|
Drug: Sitagliptin
100 mg once daily in the morning
Drug: Metformin
up to 2000 mg/day
|
Treatment D: Placebo Comparator
placebo
|
Drug: Placebo
500mg 1-0-0-0
Drug: Placebo
100mg 1-0-0-0
|
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.
Ages Eligible for Study: | 30 Years to 75 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Germany | |
Diabeteszentrum Bad Lauterberg | |
Bad Lauterberg, Germany, 37431 |
Principal Investigator: | Michael A. Nauck, Prof. Dr. | Diabeteszentrum Bad Lauterberg |
Responsible Party: | Diabeteszentrum Bad Lauterberg ( Prof. Dr. M. Nauck ) |
Study ID Numbers: | DZBL 2008-01, EudraCT: 2008-001663-11 |
Study First Received: | May 21, 2008 |
Last Updated: | May 23, 2008 |
ClinicalTrials.gov Identifier: | NCT00683735 |
Health Authority: | Germany: Ethics Commission |
Incretin, DPP-4, metformin, sitagliptin, insulin secretion |
Metformin Diabetes Mellitus Insulin Sitagliptin |
Dipeptidyl-Peptidase IV Inhibitors Hypoglycemic Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs |
Enzyme Inhibitors Pharmacologic Actions Protease Inhibitors |