Antidiabetic Effects of Adding a DPP-4 Inhibitor (Sitagliptin) to Pre-Existing Treatment With an Incretin Mimetic (Liraglutide) in Patients With Type 2 Diabetes Treated With Metformin
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Type 2 Diabetes
- Sponsor
- Michael A. Nauck
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)
- Status
- Completed
- Last Updated
- 9 years ago
Overview
Brief Summary
Objectives: To quantify differences in control of glycemia (primary objective) and the secretion of endogenous incretin hormones (secondary objective) comparing sitagliptin or placebo added to pre-existing therapy with liraglutide and metformin
Detailed Description
This is a double blind, controlled, cross-over comparison of adding sitagliptin (or placebo) to pre-existing metformin+liraglutide therapy. Patients with type 2 diabetes mellitus (T2DM) on pre-existing treatment with metformin (≥ 1500 mg/d) monotherapy or metformin plus liraglutide (1.2 mg/d) will be studied. Patients on metformin monotherapy will, after screening and randomization, enter a run-in period of 2 weeks with the additional treatment of liraglutide (0.6 mg/d for 1 week followed by 1.2 mg/d for another week). At the end of this 2 weeks therapy, a mixed meal challenge will take place, with the assessment of glucose and hormone responses (insulin, C-peptide, glucagon, GLP-1 \[glucagon-like peptide-1\], GIP (gastric inhibitory peptide) and gastric emptying as measured by 13C (carbon 13)-octanoate breath tests. Prior to the meal tests, liraglutide will be administered at a dose of 1.2 mg per injection, which is the recommended dose for treatment. Sitagliptin will be used at a dose of 100 mg, which is recommended for clinical use.
Investigators
Michael A. Nauck
Prof. Dr. med.
Diabeteszentrum Bad Lauterberg im Harz
Eligibility Criteria
Inclusion Criteria
- •Signed \& dated written informed consent
- •Male \& female subjects with a diagnosis of type 2 diabetes mellitus according to ADA criteria at least 4 months prior to screening
- •Medical history without major pathology (with the exception of type 2 diabetes) as judged by the investigator
- •On a stable regimen of metformin for at least 1 month and liraglutide 1.2 mg for at least 1 week at the time-point of randomisation.
- •Age: 25 - 75 years, both inclusive
- •Body mass index (BMI): 22 - 40kg/m\^2, both inclusive
- •HbA1c ≥ 6.5 and ≤ 8.5% (≥ 7.0 and ≤ 8.5% for patients without previous liraglutide treatment)
- •Female must be post-menopausal, surgically sterilized or practicing an effective birth control
- •Exclusion criteria
- •Subjects with type 1 diabetes, maturity onset diabetes of the young (MODY) or secondary forms of diabetes such as due to pancreatitis
Exclusion Criteria
- Not provided
Arms & Interventions
Sitagliptin, then Placebo
Intervention: Placebo
Sitagliptin, then Placebo
Intervention: Mixed meal test
Sitagliptin, then Placebo
Intervention: Liraglutide
Sitagliptin, then Placebo
Intervention: Sitagliptin
Placebo, then Sitagliptin
Intervention: Placebo
Placebo, then Sitagliptin
Intervention: Mixed meal test
Placebo, then Sitagliptin
Intervention: Liraglutide
Placebo, then Sitagliptin
Intervention: Sitagliptin
Outcomes
Primary Outcomes
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)
Time Frame: 0 to 300 min post mixed meal test
Incremental area under the plasma glucose (BG) concentration-time profile (AUC) immediately before to 300 min after a mixed meal test. In addition, the time course of BG values will be analysed with an ANCOVA model for repeated measurements with placebo baseline values as covariate. Time points to create the curce were 0, 15, 30, 45, 60, 90, 120, 150, 180, 240 and 300 minutes post mixed meal test.
Secondary Outcomes
- AUC Active GLP-1(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Plasma Glucose(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Insulin(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC C-peptide(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Glucagon(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Total GLP-1(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Total GIP(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))
- AUC Active GIP(Approximately 6 weeks (range 9 - 60 days / 8.5 weeks))