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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
16
Patients administered a single dose of placebo during a mixed meal challenge.
Subjects will be instructed to consume the mixed meal test within 20 minutes. The exact start and stop time of the mixed meal test consumption will be recorded in the CRF. The mixed meal test procedures will be identical for all subjects randomised in the study. To detect the plasma glucose excursion after mixed meal test, plasma glucose will be closely monitored
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) that will be continued for the entire duration of the study.
Diabeteszentrum Bad Lauterberg
Bad Lauterberg im Harz, Germany
Incremental Area Under the Plasma Glucose (BG) Concentration-time Profile (AUC)
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.
Time frame: 0 to 300 min post mixed meal test
AUC Plasma Glucose
Incremental AUC from 0 to 300 min
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Insulin
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC C-peptide
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Glucagon
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GLP-1
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Total GIP
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GLP-1
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
AUC Active GIP
Time frame: Approximately 6 weeks (range 9 - 60 days / 8.5 weeks)
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Patients administered a single dose of Sitagliptin during a mixed meal challenge.