A Randomized Controlled Trial to Evaluate Early Intermittent Intensive Insulin Therapy as an Effective Treatment of Type 2 Diabetes: REmission Studies Evaluating Type 2 DM - Intermittent Insulin Therapy (RESET-IT)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Mount Sinai Hospital, Canada
- Enrollment
- 109
- Locations
- 1
- Primary Endpoint
- Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).
Study Overview
Brief 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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 30 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Metformin alone
After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy. Metformin will be initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months).
Intervention: Metformin alone (Drug)
Metformin + Intermittent Insulin Therapy
After a 3-week course of intensive insulin therapy, participants will be treated with ongoing metformin monotherapy, initiated at 500mg twice a day for the first 2 weeks, before progressing to 1000mg twice a day for the duration of the trial (24 months). Participants will stop their metformin for 2 weeks every 3 months, during which time they will receive intermittent intensive insulin therapy for 2 weeks. The 2-week course of insulin therapy will be repeated at 3-, 6-, 9-, 12-, 15-,18- and 21-months, with final outcome measurement performed at 24-months.
Intervention: Metformin + Intermittent Insulin Therapy (Drug)
Outcomes
Primary Outcomes
Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).
Time Frame: 2 years
ISSI-2 is an established measure of beta-cell function. ISSI-2 is defined as the product of (i) insulin secretion measured by the ratio of the area-under-the-insulin-curve to the area-under-the-glucose curve and (ii) insulin sensitivity measured by the Matsuda index.
Secondary Outcomes
- Baseline-adjusted glycemic control at 2-years.(2 years)