Remission Evaluation of Metabolic Interventions in Type 2 Diabetes (REMIT Pilot Trial)

This is a pilot trial of 125 patients allocated to either usual care (1/3), 2 months or 4 months of intensive lifestyle and pharmacotherapy followed by cessation of all drug therapy.

Inclusion criteria

• men and women 30-80 years of age inclusive
• type 2 diabetes mellitus diagnosed by a physician within 3 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 ≤ 8.5% on no oral hypoglycemic agents or HbA1C ≤ 7.5% on 1 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 therapy
• history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance
• 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 inflammatory bowel disease, colonic ulcers, recent or significant bowel surgery, or predisposition to bowel obstruction
• cardiovascular disease including any of:

• systolic blood pressure >180 mmHg or diastolic blood pressure >105 mmHg
• peripheral vascular disease
• left bundle branch block or third degree AV block
• tachyarrhythmias or bradyarrhythmias with uncontrolled ventricular rate
• stenotic valvular heart disease
• cardiomyopathy
• history of heart failure
• history of aortic dissection
• documented history of angina or coronary artery disease
• history of stroke or transient ischemic attack
• pulmonary disease with dependence on oxygen
• history of any disease requiring intermittent or 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
• any history of excessive alcohol intake, acute or chronic
• known hypersensitivity to metformin, acarbose, or insulin glargine.