Diabetes Mellitus Type 2
Conditions
Brief summary
The study is designed to investigate the effect of 18 weeks treatment with Sitagliptin 100 mg/day on the insulin secretion capacity of beta cells. Patients who meet the study enrollment criteria will undergo 2 experiments (see description below); a graded hyperglycemic technique and a meal test, prior to randomization and after a 12-wk double-blind study period. The treatment effect will shed light on the magnitude of the beta cell capacity to increase its mass and function.
Detailed description
Study design and duration: This will be an Israeli three center study. Study drug: Sitagliptin 100 mg. The study will be a double blind, randomized two arms parallel group study. The duration of the study will be up to 18 weeks (with 8 visits) for each patient. This will include: a screening period of up to 4 weeks (Visit 1 to visit 2), a 2 week single blind, placebo run-in period (visit 2 to visit 4), and a 12 week placebo controlled, double blind treatment period (visit 4 to visit 8). Patients with T2DM who have not been treated with an AHA, or who are on AHA monotherapy or low dose oral combination therapy (low dose defined as ≤50% of the maximum labeled dose of each agent), may participate if they meet all enrollment criteria. Patients eligible to be randomized will have a HbA1c ³6.5% and £10% . Patients who meet the study enrollment criteria will undergo 2 experiments (see description below); a graded hyperglycemic technique and a meal test, prior to randomization (Visit 3 and 4). These experiments will be will be completed after a 12-hour overnight fast. The 2 experiments will be repeated at the conclusion of the 12-wk double-blind study period (Visits 7 and 8). Efficacy measurements: (1) Glycemic control : FPG, HbA1c, β-cell Function Parameters(Φs, Φd, Φb, Φ, Φob, T), Insulin Secretion Rate (determined from C-peptide deconvolution), 1st and 2nd phase insulin secretion, Insulin response after arginine injection, Insulin sensitivity index, glucose, insulin, C-peptide total and incremental area under the curve.
Interventions
DRUGsitagliptin
Sponsors
Sheba Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient has T2DM diagnosed within the past 5 years * Patient is \>18 and \<65 years of age * Patient is not pregnant, breast feeding and unlikely to conceive * Patient understands the study procedures, and agrees to participate in the study by giving written informed consent * Patient meets one of the following criteria: 1. Patient is currently not on an AHA and has a Visit 1 HbA1c ≥6.5% and ≤10%. OR 2. Patient is currently on AHA monotherapy or low dose (i.e. ≤50% maximum labeled dose of each agent) oral combination therapy and has a Screening/Visit 1 HbA1c ≥6.5% and ≤9.5%. * At visit 2, patient has a HbA1c of ≥6.5% and ≤10%
Exclusion criteria
* Patient has type 1 diabetes mellitus * Patient required insulin therapy within 12 weeks of Visit 1. Note: patients who received a brief period of insulin treatment (e.g., several days during a hospitalization) and who are no longer requiring insulin treatment may participate * Patient is currently or within 12 weeks of Visit 1 taking a TZD agent as monotherapy or in combination * Patient is currently or within 12 weeks of Visit 1 taking Byetta. * Patient is on corticosteroids * Patient has a history of malignancy ≤5 years prior to signing informed consent, or \>5 years without documentation of remission/cure Exception: Adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer. Melanoma, leukemia, lymphoma and myeloproliferative disorders of any duration are excluded -Patient is on chemotherapy * Patient received another investigational drug in the last 12 weeks. * Patients with concomitant liver disease and or AST \> 3 fold upper limit of normal * Patients with kidney disease or CR\>1.4 mg/dl * Patients with anemia ( Hb \<11 gr in male 10 gr in female) * Patient with active vascular disease (coronary, peripheral or cerebrovascular) * Patient has poorly controlled hypertension defined as systolic blood pressure \>160 mm Hg or diastolic \>95 mm Hg * Proliferative retinopathy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| FPG, | — |
| HbA1c, | — |
| β-cell Function Parameters(Φs, Φd, Φb, Φ, Φob, T), Insulin Secretion Rate (determined from C-peptide deconvolution), 1st and 2nd phase insulin secretion, Insulin response after arginine injection, Insulin sensitivity index, glucose, insulin, | — |
| C-peptide total and incremental area under the curve. | — |
Countries
Israel
Outcome results
None listed