remission evaluation of a metabolic intervention in type 2 diabetes with sitagliptin (remit-sita)

Conditions: Type 2 Diabetes Mellitus

Summary: the purpose of the study is to determine whether in patients with early type 2 diabetes,a short-term intensive metabolic intervention comprising of sitagliptin, metformin, basal insulin glargine and lifestyle approaches will be superior to standard diabetes therapy in achieving sustained diabetes remission.

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

Eligibility criteria:
inclusion criteria: 1. men and women 30-80 years of age inclusive; 2. type 2 diabetes mellitus diagnosed by a physician within 5 years prior to patient enrollment; 3. anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization; 4. hba1c ≤ 9.5% on no oral hypoglycemic agents or hba1c ≤ 8.0% on 1 oral agent or on half-maximal doses of 2 agents; 5. body mass index ≥ 23 kg/m2; 6. 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; 7. ability and willingness to perform self-monitoring of capillary blood glucose (smbg); ability and willingness to self-inject insulin; 8. provision of informed consent. exclusion criteria: 1. current use of insulin; 2. history of hypoglycemia unawareness; history of severe hypoglycemia requiring assistance within the last 5 years; 3. renal dysfunction as evidenced by serum creatinine (cr) ≥ 124 μmol/l; 4. history of lactic acidosis or diabetic ketoacidosis; 5. active liver disease or elevated alanine transferase (alt) levels ≥ 2.5 times upper limit of normal at the time of enrollment; 6. history of pancreatitis; 7. 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; 8. history of any disease requiring continuous systemic glucocorticoid treatment; 9. history of any major illness with a life expectancy of \< 3 years; 10. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity; 11. excessive alcohol consumption (\>14 alcoholic drinks per week in men and \>7 alcoholic drinks per week in women); 12. known hypersensitivity to insulin glargine, metformin, or any dpp-4 inhibitor.

Keywords: diabetes insulin glargine metformin sitagliptin diet excercise lifestyle