Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Sitagliptin (REMIT-Sita)

This is a multicentre, open-label, randomized controlled trial in 100 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 12-week course of treatment with sitagliptin, metformin, insulin glargine and lifestyle therapy, or (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 meet criteria for hyperglycemic 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 30-80 years of age inclusive;
• type 2 diabetes mellitus diagnosed by a physician within 5 years prior to patient enrollment;
• anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization;
• HbA1C ≤ 9.5% on no oral hypoglycemic agents or HbA1C ≤ 8.0% on 1 oral agent or on half-maximal doses of 2 agents;
• body mass index ≥ 23 kg/m2;
• a negative pregnancy test and an agreement to use a reliable method of birth control for the duration of the trial in all females with childbearing potential;
• ability and willingness to perform self-monitoring of capillary blood glucose (SMBG); ability and willingness to self-inject insulin;
• provision of informed consent.

Exclusion criteria

• current use of insulin;
• history of hypoglycemia unawareness; history of severe hypoglycemia requiring assistance within the last 5 years;
• renal dysfunction as evidenced by serum creatinine (Cr) ≥ 124 μmol/l;
• 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 enrollment;
• history of pancreatitis;
• cardiovascular disease including any of: a) systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg; b) peripheral vascular disease; c) left bundle branch block or second or third degree AV block; d) tachyarrhythmias or bradyarrhythmias with uncontrolled ventricular rate; e) stenotic valvular heart disease; f) cardiomyopathy; g) history of heart failure; h) history of aortic dissection; i) documented history of angina or coronary artery disease; j) history of stroke or transient ischemic attack;
• history of any disease requiring continuous systemic glucocorticoid treatment;
• 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 consumption (>14 alcoholic drinks per week in men and >7 alcoholic drinks per week in women);
• known hypersensitivity to insulin glargine, metformin, or any DPP-4 inhibitor.