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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: IDegLira
* Drug: insulin degludec
* Drug: Metformin
* Behavioral: Lifestyle Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, IDegLira, Metformin, Insulin, Diet, Excercise, Lifestyle