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

Phase 3CompletedNCT02192424

Mount Sinai Hospital, Canada109 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

109

Conditions

Type 2 Diabetes

Interventions

Eligibility

Sex: ALLMin age: 30 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Baseline-adjusted beta-cell function at 2 years, measured by Insulin Secretion-Sensitivity Index-2 (ISSI-2).

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.

Time frame: 2 years

Secondary Outcomes

Baseline-adjusted glycemic control at 2-years.

The secondary outcome of baseline-adjusted glycemic control at 2-years will be assessed by A1c (glycated hemoglobin)