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

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 iGlarLixi, 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 12-week course of treatment with iGlarLixi, metformin and lifestyle therapy, and (b) standard diabetes therapy, and followed for a total of 64 weeks (1 year and 3 months). In all participants with HbA1C<7.3% at the 12 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 IGlarLixi

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: iGlarLixi
* Drug: Insulin Glargine
* 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; type 2 diabetes mellitus within 5 years of diagnosis; stable diabetes drug regimen in the 10 weeks before randomization; HbA1c 6.5-9.5% on no glucose lowering drugs, or </= 8.5% on 1 glucose-lowering drug, or </= 8.0% on 2 glucose lowering drugs; body mass index >/= 23 kg/m2; ability and willingness to perform self-monitoring of capillary blood glucose (SMBG); ability and willingness to self-inject iglarlixi; and 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 renal dysfunction as evidenced by eGFR<45 mL/min/1.73 m2 by MDRD formula; history of lactic acidosis or diabetic ketoacidosis; active liver disease or elevated alanine transferase (ALT) levels >\= 2.5 times upper limit of normal at the time of enrolment; history or clinical suspicion of pancreatitis or medullary thyroid cancer, or a calcitonin level >/= 20 pg/ml; 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 glargine, lixisenatide 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: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise | Drug: iGlarLixi<br>* Dose is titrated to achieve fasting normoglycemia<br>* Other names: glargine insulin / lixisenatide;Drug: Insulin Glargine<br>* In those who need additional insulin or who cannot tolerate iGlarLixi, insulin glargine will be used. Dose is titrated to achieve fasting normoglycemia.<br>* Other names: Lantus;Drug: Metformin<br>* Dose is titrated to 2000 mg daily or maximal tolerated dose<br>Behavioral: Lifestyle therapy<br>* Lifestyle intervention includes individualized dietary and exercise advice and frequent visits 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 |
| --- | --- | --- |
| The first occurrence of diabetes relapse |  | 64 weeks of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants achieving drug-free diabetes remission | Diabetes remission is defined as HbA1C < 6.5% off diabetes drugs for at least 12 weeks | 24 weeks after randomization | 
| Number of participants achieving drug-free normoglycemia defined as HbA1C < 6.0% off diabetes drugs for at least 12 weeks |  | 24 weeks after randomization | 
| Percentage of weight loss from baseline | (Weight at randomization - weight at 12 weeks)/(weight at randomization) | 12 weeks | 
| Change in waist circumference from baseline | (Waist circumference at 12 weeks - weight circumference at randomization) | 12 weeks | 
| Glycated hemoglobin (HbA1C) | Expressed in Diabetes Control and Complications Trial (DCCT) units | 12 weeks | 

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