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

Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira (REMIT IDegLira): A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: IDegLira; Drug: insulin degludec; Drug: Metformin; Behavioral: Lifestyle Therapy

Detailed Description

This is a multicentre, open-label, randomized controlled trial in 160 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 16-week course of treatment with IDegLira, metformin and lifestyle therapy, and (b) standard diabetes therapy, and followed for a total of 68 weeks (1 year and 4 months). In all participants with HbA1C<7.3% at the 16 week visit, glucose-lowering medications will be discontinued and participants will be encouraged to continue with lifestyle modifications and regular glucose monitoring. Participants with HbA1C ≥ 7.3% at this visit or who experience hyperglycemia relapse after stopping drugs will receive standard glycemic management as informed by the current Canadian Diabetes Association clinical practice guidelines.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2E1
      • University of Alberta
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Hospital
    • London, Ontario, Canada, N6G 2M1
      • Western University
    • Oakville, Ontario, Canada, L6M 1M1
      • LMC Manna Research
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 26 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. current use of insulin therapy;
2. history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
3. history of end-stage renal disease or eGFR<45 mL/min/1.73 m2 by MDRD formula;
4. active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times the upper limit of normal at the time of enrolment;
5. history or clinical suspicion of pancreatitis or medullary thyroid cancer;
6. diagnosis or first degree relative with Multiple Endocrine Neoplasia Type 2 (MEN2);
7. history of diabetic retinopathy requiring photocoagulation, injection therapy or vitrectomy;
8. 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).
9. history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
10. history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
11. history of any major illness with a life expectancy of < 3 years;
12. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
13. excessive alcohol intake, acute or chronic;
14. 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;
15. inability to take insulin degludec, liraglutide or metformin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard Care; Standard glycemic care as informed by the current clinical practice guidelines
Experimental: Intervention; Drug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise	Drug: IDegLira; Dose is titrated to achieve fasting normoglycemia; Other Names: insulin degludec / liraglutide; Drug: insulin degludec; In those who need additional insulin or who cannot tolerate IDegLira, insulin degludec will be used. Dose is titrated to achieve fasting normoglycemia.; Drug: Metformin; Dose is titrated to 2000 mg per day or maximal tolerated dose; Behavioral: Lifestyle Therapy; 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; Other Names: diet and exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	defined as HbA1C < 6.0% off glucose-lowering agents for at least 12 weeks.	28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
Proportion of participants achieving drug-free diabetes regression	defined as HbA1C <7.0% off glucose-lowering agents for at least 12 weeks.	28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

Other Outcome Measures

Outcome Measure	Time Frame
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
the change in weight	16, 28, 40, 52 and 68 week visit as well as the overall change
the change in waist circumference	16, 28, 40, 52 and 68 week visit as well as the overall change
the change in hip circumference	16, 28, 40, 52 and 68 week visit as well as the overall change
the change in body mass index	16, 28, 40, 52 and 68 week visit as well as the overall change
the change in coefficient of variation over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear	from randomization until the 6, 16, 28 and 52 week visit
the change in interquartile range over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear	from randomization until the 6, 16, 28 and 52 week visit
the change in time range over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear	from randomization until the 6, 16, 28 and 52 week visit

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Novo Nordisk A/S
• Investigators: Principal Investigator: Zubin Punthakee, MD, McMaster University; Study Chair: Hertzel Gerstein, MD, McMaster University

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2019
• Primary Completion (Actual): June 15, 2022
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 5, 2019

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Metformin; Diet; Lifestyle; IDegLira; Excercise
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Insulin; Insulin, Globin Zinc; Insulin, Long-Acting; Liraglutide; Metformin; Xultophy
• Other Study ID Numbers: REMITiDegLira

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No