effect of januvia on beta cell function in patients with diabetes mellitus

Conditions: Diabetes Mellitus Type 2

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.

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.

Eligibility criteria:
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