Beta-Cell Function and Sitagliptin Trial (BEST)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus, Type 2
Intervention: Sitagliptin; Placebo; metformin
Intervention description: sitagliptin 100 mg once a day; placebo once a day; metformin 1000 mg twice a day (bid) by mouth (po)
Intervention MeSH terms: Metformin; Sitagliptin Phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 30 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Type 2 diabetes; beta-cell function; sitagliptin; intensive insulin therapy

Summary:

      Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by progressive
      deterioration in the function of the pancreatic beta-cells, which are the cells that produce
      and secrete insulin (the hormone primarily responsible for the handling of glucose in the
      body). The investigators propose a double-blind, randomized controlled pilot study comparing
      the effect of sitagliptin (a novel anti-diabetic drug with beta-cell protective potential)
      versus placebo, on the preservation of beta-cell function over one year in patients with T2DM
      on metformin, the first-line agent for the treatment of T2DM (ie. the study groups will be
      (i) sitagliptin and metformin versus (ii) placebo and metformin). This study may demonstrate
      an important beta-cell protective capacity of sitagliptin.

      Hypothesis: In patients with T2DM on metformin, treatment with the DPP-IV inhibitor
      sitagliptin will preserve pancreatic beta-cell function.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Men and women between the ages of 30 and 75 inclusive

          2. Physician-diagnosed type 2 diabetes on 0-2 oral hypoglycemic agents

          3. Negative for anti-glutamic acid decarboxylase (anti-GAD_ antibodies (to rule out
             Latent Autoimmune Diabetes of Adults (LADA)

          4. A1c at screening between 6.5% and 9% inclusive if on no oral hypoglycemic agents or
             6.0% and 9.0% inclusive if on 1-2 oral hypoglycemic agents

        Exclusion Criteria:

          1. Current insulin therapy

          2. Type 1 diabetes or secondary forms of diabetes

          3. Any major illness with a life expectancy of < 5 years or that may interfere with the
             patient's participation in the study

          4. Involvement in any other study requiring drug therapy

          5. Renal dysfunction as evidenced by serum creatinine >/= 136 umol/L for males or >/= 124
             umol/L for females or abnormal creatinine clearance (< 60 ml/min by Modification of
             Diet in Renal Disease (MDRD) formula)

          6. Hepatic disease considered to be clinically significant (includes jaundice, chronic
             hepatitis, or previous liver transplant) or transaminases > 2.5 times the upper limit
             of normal

          7. Excessive alcohol consumption, defined as > 14 alcoholic drinks per week for males and
             > 9 alcoholic drinks per week for females

          8. Pregnancy or unwillingness to use reliable contraception. Women should not be planning
             pregnancy for the duration of the study. Reliable contraception includes: birth
             control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or
             condoms with spermicide. Any women who miss a menstrual period or think that they may
             be pregnant must have a pregnancy test as soon as possible

          9. History of serious arrhythmia or atrioventricular block on baseline electrocardiogram

         10. Uncontrolled hypertension (systolic blood pressure > 180 mm Hg or diastolic blood
             pressure > 110 mm Hg)

         11. Unwillingness to undergo multiple daily insulin injection therapy for 4 weeks

         12. Unwillingness to perform capillary blood glucose monitoring at least 4 times per day
             during intensive insulin therapy