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

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.

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