beta-cell function and sitagliptin trial (best)

Conditions: Type 2 Diabetes Mellitus

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.

medications currently used in the treatment of t2dm have not been shown to modify the progressive decline in beta-cell function that occurs over time. recent evidence, however, suggests that a new class of anti-diabetic medications, called dipeptidyl peptidase-iv (dpp-iv) inhibitors, may be able to protect beta cells and hence alter the natural history of t2dm. we thus wish to study the effect of sitagliptin (a dpp-iv inhibitor) on the preservation of beta-cell function in patients with t2dm randomized to either (i) sitagliptin and metformin or (ii) placebo and metformin.

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

Keywords: type 2 diabetes beta-cell function sitagliptin intensive insulin therapy