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

• Proportion of participants achieving normoglycemia in the experimental group 1 compared to the control group [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
• Proportion of participants achieving normoglycemia in the experimental group 2 compared to the control group [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

• Proportion of participants with normal glucose tolerance [ Time Frame: 20 and 28 weeks ] [ Designated as safety issue: No ]
• Proportion of participants with normal fasting plasma glucose [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Change in fasting plasma glucose from baseline [ Time Frame: Baseline and 52 weeks ] [ Designated as safety issue: No ]
• HbA1C [ Time Frame: 8, 20, 28 and 52 weeks ] [ Designated as safety issue: No ]
• Change in weight from baseline [ Time Frame: Baseline, 8, 20, 28 and 52 weeks ] [ Designated as safety issue: No ]
• Rate of symptomatic hypoglycemic episodes [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
• Rate of severe hypoglycemic episodes [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

• Proportion of participants with normal glucose tolerance [ Time Frame: 20 and 28 weeks ] [ Designated as safety issue: No ]
• Proportion of participants with normal fasting plasma glucose [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• Change in fasting plasma glucose from baseline [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
• HbA1C [ Time Frame: 8, 20, 28 and 52 weeks ] [ Designated as safety issue: No ]
• Change in weight from baseline [ Time Frame: 8, 20, 28 and 52 weeks ] [ Designated as safety issue: No ]
• Rate of symptomatic hypoglycemic episodes [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]
• Rate of severe hypoglycemic episodes [ Time Frame: 28 weeks ] [ Designated as safety issue: Yes ]

The purpose of this pilot trial is to determine whether an intensive treatment with insulin glargine, metformin, acarbose and lifestyle can normalize blood glucose levels in patients with recently diagnosed type 2 diabetes mellitus when compared to standard diabetes care.

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.

• Drug: insulin glargine
  sc injection
• Drug: metformin
  oral administration
• Drug: acarbose
  oral administration
• Behavioral: lifestyle therapy
  diet and exercise
• Other: Standard glycemic care
  as informed by the current clinical practice guidelines

• Experimental: Group 1 (short)
  Interventions:

  • Drug: insulin glargine
  • Drug: metformin
  • Drug: acarbose
  • Behavioral: lifestyle therapy
• Experimental: Group 2 (long)
  Interventions:

  • Drug: insulin glargine
  • Drug: metformin
  • Drug: acarbose
  • Behavioral: lifestyle therapy
• Standard care
  Intervention: Other: Standard glycemic care

Inclusion Criteria:

1. men and women 30-80 years of age inclusive
2. type 2 diabetes mellitus diagnosed by a physician within 3 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 6.5-8% inclusive on no oral hypoglycemic agents or HbA1C ≤ 7.5% on 1 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)
8. ability and willingness to self-inject insulin
9. provision of informed consent.

Exclusion Criteria:

1. current use of insulin therapy
2. history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance
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 inflammatory bowel disease, colonic ulcers, recent or significant bowel surgery, or predisposition to bowel obstruction

7. 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
8. pulmonary disease with dependence on oxygen
9. history of any disease requiring intermittent or continuous systemic glucocorticoid treatment
10. history of any major illness with a life expectancy of <3 years
11. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity
12. any history of excessive alcohol intake, acute or chronic
13. known hypersensitivity to metformin, acarbose, or insulin glargine.