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

NCT ID: NCT02192424

Last Updated: 2020-10-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 109 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2020-09-30

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Metformin alone

Intervention Type: 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.

Group Type: EXPERIMENTAL

Metformin + Intermittent Insulin Therapy

Intervention Type: DRUG

Interventions

Metformin alone

Intervention Type: DRUG

Metformin + Intermittent Insulin Therapy

Intervention Type: DRUG

Other Intervention Names

metformin; metformin,; basal insulin glargine and pre-meal insulin lispro

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Canadian Institutes of Health Research (CIHR)

OTHER_GOV

Sponsor Role: collaborator

Mount Sinai Hospital, Canada

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ravi Retnakaran, MD

Role: PRINCIPAL_INVESTIGATOR

MOUNT SINAI HOSPITAL

Locations

Mount Sinai Hospital

Toronto, Ontario, Canada

Countries

Canada

References

Retnakaran R, Pu J, Emery A, Harris SB, Reichert SM, Gerstein HC, McInnes N, Kramer CK, Zinman B. Determinants of sustained stabilization of beta-cell function following short-term insulin therapy in type 2 diabetes. Nat Commun. 2023 Jul 27;14(1):4514. doi: 10.1038/s41467-023-40287-w.

Reference Type: DERIVED

PMID: 37500612 (View on PubMed)

Other Identifiers

12-0263-A Main

Identifier Type: -

Identifier Source: org_study_id