Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM
Condition: Diabetes
MeSH terms: Diabetes Mellitus
Intervention: Sitagliptin; Metformin; Sitagliptin + Metformin; Placebo
Intervention description: tablet, 100 mg/day, 6 weeks; tablet, 1000 mg/ bid, 6 weeks; tablet, Sitagliptin (100mg/day) + tablet, Metformin (1000 mg/bid), 6 weeks; Placebo 6 weeks
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Diabetes

Summary:

      In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after
      6 weeks of treatment:

      Objective: To assess the effects of co-administration of sitagliptin and metformin compared
      to placebo on hepatic glucose production (HGP).

      Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin
      provides greater reduction in hepatic glucose production (HGP) compared to placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must meet all of the following inclusion criteria to participate in the
             study.

          -  Patients with screening values/findings outside ranges described in the protocol may
             have one repeat determination performed and if the repeat value satisfies the
             criterion, they may continue in the screening process.

          -  If the repeat value does not satisfy the criterion, the principal investigator will
             review the abnormal laboratory value and decide whether the subject may continue in
             the screening process.

          -  All screening laboratory measurements are to be performed after an overnight fast ≥10
             hours in duration.

          -  Patients must be able to communicate meaningfully with the investigator and must be
             legally competent to provide written informed consent.

          -  Patients can be either male or female.

          -  Patients are ≥18 and ≤70 years of age on the day of signing informed consent.

          -  Patients must meet the current American Diabetes Association criteria for the
             diagnosis of type 2 diabetes mellitus

          -  Patients must be on diet or diet plus exercise therapy.

          -  Patients must have a HbA1c ≥ 7.5% and ≤ 9.5%

          -  Patients must have a BMI of 23-40 kg/m2

          -  Patients must have the following laboratory values:

               -  Hematocrit Males ≥ 34 vol%

               -  Females ≥ 33vol%

               -  Serum creatinine ≤ 1.5 mg/dL in males and ≤ 1.4 mg/dL in females

               -  AST (SGOT): ≤ 2.5 times upper limit of normal

               -  ALT (SGPT): ≤ 2.5 times upper limit of normal

               -  Alkaline phosphatase ≤ 2.5 times upper limit of normal

               -  If serum creatinine is > 1.5 mg/dl in males and > 1.4 mg/dl in females, the
                  Principal Investigator can include the patient if the measured GFR is >70 ml/min
                  (24 hour creatinine clearance)

          -  Patients must have been on a stable dose of allowed chronic medications for ≥30 days
             prior to entering the study.

          -  Only patients whose body weight has been stable (±4 pounds) over the three months
             prior to the study will be included.

        Exclusion Criteria:

          -  Patients are excluded from participation in the study if they meet any of the
             following criteria:

               -  Patient has type 1 diabetes.

               -  Patient has received insulin for more than one week within the previous year
                  prior to entry.

               -  Patient has been treated with exenatide or a non-TZD, oral antihyperglycemic
                  agent within the last 2 months or with a TZD (pioglitazone or rosiglitazone)
                  within the last 4 months.

               -  Patient is receiving any medications with known adverse effects on glucose
                  tolerance (e.g., systemic glucocorticoids, psychotropic drugs like clozapine,
                  olanzapine, haloperidol, risperidone). Note: Patients may be taking stable doses
                  of estrogens, other hormonal replacement therapy, or lipid and blood pressure
                  lowering agents if the patient has been on these agents for the prior three
                  months.

               -  Patient has evidence of a significant cardiovascular disorder within 6 months of
                  signing informed consent (e.g. acute coronary syndrome, coronary artery
                  intervention, stroke or transient ischemic neurological disorder) or has New York
                  Heart Association Classification greater than Class 2; or has significant
                  findings on ECG (other than non-specific ST-T wave changes); or peripheral
                  vascular disease (history of claudication); or has dyspnea on exertion of one
                  flight or less, or abnormal breath sounds on auscultation.

               -  Patient has a history of intolerance or hypersensitivity to a DPP-4 inhibitor or
                  to metformin.

               -  Patient is pregnant or plans to become pregnant within the projected duration of
                  the study.