Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes (RESET-IT Main Trial)

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.

Inclusion criteria

• Men and women between the ages of 30 and 80 years inclusive
• T2DM diagnosed by a physician </= 5 years prior to enrolment
• Negative for anti-glutamic acid decarboxylase (anti-GAD) antibodies
• On either no anti-diabetic medication or on metformin monotherapy, with no change in dose/regimen within 4 weeks prior to enrolment
• 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
• BMI >/= 23 kg/m2
• Negative pregnancy test at recruitment for all women with childbearing potential

Exclusion criteria

• Current anti-diabetic treatment with insulin, sulfonylurea, thiazolidinedione, alpha-glucosidase inhibitor, glucagon-like peptide-1 (GLP-1) agonist or dipeptidyl peptidase-4 inhibitor
• Type 1 diabetes or secondary forms of diabetes
• History of hypoglycemia unawareness or severe hypoglycemia requiring assistance
• Any major illness with a life expectancy of <5 years
• Hypersensitivity to insulin, metformin or the formulations of these products
• Renal dysfunction as evidenced by estimated glomerular filtration rate (eGFR) <50 ml/min
• Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, previous liver transplant) or transaminases >2.5 X upper limit of normal
• History of congestive heart failure
• Excessive alcohol consumption, defined as >14 alcoholic drinks per week for males and >9 alcoholic drinks per week for females
• Unwillingness to administer insulin therapy or perform capillary blood glucose monitoring at least 4 times per day while receiving IIT
• 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.
• Non-adherence to the induction phase or any factor likely to limit adherence to the study protocol, in the opinion of the investigator