early intermittent intensive insulin therapy as an effective treatment of type 2 diabetes (reset-it main trial)

Conditions: Type 2 Diabetes

Summary: type 2 diabetes mellitus 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 randomized controlled trial to determine whether intermittent intensive insulin therapy is an effective therapeutic strategy that can preserve pancreatic beta-cell function and maintain glycemic control early in the course of type 2 diabetes.

in this study, eligible patients with type 2 diabetes will be randomized to either intermittent insulin therapy or not, on a background of metformin, after first undergoing a short course of intensive insulin therapy. the hypothesis under study is whether intermittent insulin therapy can preserve beta-cell function.

Eligibility criteria:
inclusion criteria: 1. men and women between the ages of 30 and 80 years inclusive 2. t2dm diagnosed by a physician \</= 5 years prior to enrolment 3. negative for anti-glutamic acid decarboxylase (anti-gad) antibodies 4. on either no anti-diabetic medication or on metformin monotherapy, with no change in dose/regimen within 4 weeks prior to enrolment 5. a1c at screening between 5.5% and 9.0% inclusive if on metformin, or between 6.0% and 9.5% inclusive if on no oral anti-diabetic medication 6. bmi \>/= 23 kg/m2 7. negative pregnancy test at recruitment for all women with childbearing potential exclusion criteria: 1. current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, glucagon-like peptide-1 (glp-1) agonist or dipeptidyl peptidase-4 inhibitor 2. type 1 diabetes or secondary forms of diabetes 3. history of hypoglycemia unawareness or severe hypoglycemia requiring assistance 4. any major illness with a life expectancy of \<5 years 5. hypersensitivity to insulin, metformin or the formulations of these products 6. renal dysfunction as evidenced by estimated glomerular filtration rate (egfr) \<50 ml/min 7. hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, previous liver transplant) or transaminases \>2.5 x upper limit of normal 8. history of congestive heart failure 9. excessive alcohol consumption, defined as \>14 alcoholic drinks per week for males and \>9 alcoholic drinks per week for females 10. unwillingness to administer insulin therapy or perform capillary blood glucose monitoring at least 4 times per day while receiving iit 11. pregnancy or unwillingness to use reliable contraception. women should not be planning pregnancy for the duration of the study or the first 3 months after the study. reliable contraception includes birth control pill, intra-uterine device, abstinence, tubal ligation, partner vasectomy, or condoms with spermicide. 12. non-adherence to the induction phase or any factor likely to limit adherence to the study protocol, in the opinion of the investigator

Keywords: beta-cell function, type 2 diabetes, intermittent insulin