Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira

NCT03862716 | Completed Phase 3

• 1 other identifier: REMITiDegLira
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 8

Brief Summary

The purpose of the study is to determine whether in patients with early type 2 diabetes, a short-term intensive metabolic intervention comprising IDegLira, metformin, and lifestyle approaches will be superior to standard diabetes therapy in achieving sustained diabetes remission.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes; IDegLira; Metformin; Insulin; Diet; Excercise; Lifestyle

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving drug-free diabetes remission

  Drug-free diabetes remission is defined as HbA1C \< 6.5 % off glucose-lowering agents for at least 12 weeks.

  28 weeks after randomization

Secondary Outcomes (3)

• Proportion of participants achieving drug-free diabetes remission

  28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

• Proportion of participants achieving drug-free normoglycemia

  28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

• Proportion of participants achieving drug-free diabetes regression

  28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

Other Outcomes (10)

• the time interval from randomization until any glucose lowering drug is restarted or relapse of hyperglycemia

  Up to week 68

• the time interval from the 16 week visit (i.e. when glucose lowering drugs are to be stopped) until any glucose lowering drug is restarted or relapse of hyperglycemia

  Up to week 68

• the change in HbA1c

  16, 28, 40, 52 and 68 week visit as well as the overall change

Study Arms (2)

Intervention

EXPERIMENTAL

Drug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise

Drug: IDegLira; Drug: insulin degludec; Drug: Metformin; Behavioral: Lifestyle Therapy

Standard Care

NO INTERVENTION

Standard glycemic care as informed by the current clinical practice guidelines

Interventions

IDegLira DRUG

Dose is titrated to achieve fasting normoglycemia

Also known as: insulin degludec / liraglutide

Intervention

insulin degludec DRUG

In those who need additional insulin or who cannot tolerate IDegLira, insulin degludec will be used. Dose is titrated to achieve fasting normoglycemia.

Intervention

Metformin DRUG

Dose is titrated to 2000 mg per day or maximal tolerated dose

Intervention

Lifestyle Therapy BEHAVIORAL

Lifestyle intervention includes individualized dietary and exercise advice targeting at least 5% weight loss with frequent visits and coaching for goal reinforcement, behavior modification and problem-solving

Also known as: diet and exercise

Intervention

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men and women aged 30-80 years;
• T2D diagnosed within 5 years
• stable T2D drug regimen in the 8 weeks before randomization;
• HbA1c 6.5-9.5% on no glucose lowering drugs, or 6.5%-8.0% on up to 2 glucose lowering drugs;
• body mass index ≥ 23 kg/m2;
• ability and willingness to perform self-monitoring of capillary blood glucose (SMBG);
• willingness to wear a continuous glucose monitor on at least 3 occasions;
• ability and willingness to self-inject IDegLira and insulin;
• provision of informed consent.

You may not qualify if:

• current use of insulin therapy;
• history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
• history of end-stage renal disease or eGFR\<45 mL/min/1.73 m2 by MDRD formula;
• active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times the upper limit of normal at the time of enrolment;
• history or clinical suspicion of pancreatitis or medullary thyroid cancer;
• diagnosis or first degree relative with Multiple Endocrine Neoplasia Type 2 (MEN2);
• history of diabetic retinopathy requiring photocoagulation, injection therapy or vitrectomy;
• history of cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including: i. acute coronary syndrome, hospitalization for unstable angina, myocardial infarction, or revascularization with coronary artery bypass grafting or percutaneous coronary intervention; ii. peripheral vascular disease, valvular heart disease, cardiomyopathy, aortic dissection, tachyarrhythmias, bradyarrhythmias, prior stroke or TIA; iii. prior hospitalization for heart failure; or iv. ECG findings concerning for ischemic heart disease (i.e. pathological Q-waves, ST-segment-T-wave abnormalities in contiguous leads, left anterior hemiblock, left bundle branch block, second or third degree atrioventricular block).
• history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
• history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
• history of any major illness with a life expectancy of \< 3 years;
• history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
• excessive alcohol intake, acute or chronic;
• currently pregnant, or breastfeeding, or not using a reliable method of birth control for the duration of the trial in all females with childbearing potential;
• inability to take insulin degludec, liraglutide or metformin.

Sponsors & Collaborators

• Population Health Research Institute: lead
• Novo Nordisk A/S: collaborator

Study Sites (8)

University of Calgary

Calgary, Alberta, T2T 5C7, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2E1, Canada

Location

Nova Scotia Health Authority

Halifax, Nova Scotia, B3H 1V7, Canada

Location

McMaster University

Hamilton, Ontario, Canada

Location

St. Joseph's Hospital

London, Ontario, N6A 4V2, Canada

Location

Western University

London, Ontario, N6G 2M1, Canada

Location

LMC Manna Research

Oakville, Ontario, L6M 1M1, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance

Interventions

IDegLira; insulin degludec; Metformin; Diet; Exercise

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Zubin Punthakee, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Hertzel Gerstein, MD

  McMaster University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: March 5, 2019
• Study Start: April 23, 2019
• Primary Completion: June 15, 2022
• Study Completion: July 31, 2023
• Last Updated: October 25, 2023

Record last verified: 2023-10

Locations

CA (8)