Glycemic Control and Complications in Diabetes Mellitus Type 2 (VADT)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Insulin; Glimepiride; Rosiglitazone; Metformin
Intervention description: Insulin (intermediate or long-lasting) in a.m. 1 unit 9 lbs Arm 1 Insulin (intermediate or long-lasting) in a.m. 1 unit 9 lbs, add one injection of insulin Arm 2; Glimepiride 2 mg Arm 1 Glimepiride 8 mg Arm 2; Rosiglitazone 4 mg Arm 1 Rosiglitazone 4 mg bid Arm 2; Metformin 500 mg (go up to 1000 mg) Arm 1 Metformin 500 mg (go up to 2000 mg) Arm
Intervention MeSH terms: Metformin; Glimepiride; Rosiglitazone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 1791.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No
Keywords: DM; glycemic control; insulin; type 2 diabetes mellitus

Summary:

      This study is a prospective, 2-arm, randomized controlled trial to determine whether glycemic
      control, achieved through intensification of treatment, is effective in preventing clinical
      macrovascular complications in patients with type 2 DM who are no longer responsive to oral
      agents alone. The study consists of a two-year accrual period and five years of follow-up (7
      years total) of 1700 patients across 20 centers. We have powered the study to detect a 21%
      reduction in the primary event rate. Additional study goals are to determine whether the
      expenditures, discomfort, and adverse effects associated with intensive intervention are
      justified in terms of their clinical benefits, considering both macrovascular and
      microvascular complications.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with type 2 DM who are no longer responsive to maximum dose of one or more
             oral agents.

        Exclusion Criteria:

          -  Angina pectoris, Canadian Class I-II,

          -  congestive heart failure, Class III-IV,

          -  stroke, incapacitating or in last 6 months,

          -  Myocardial infarction (MI) or invasive cardiovascular procedure within the past six
             months,

          -  ongoing diabetic gangrene,

          -  BMI > 40,

          -  hemoglobinopathy that interferes with A1c monitoring,

          -  serum creatinine > 1.6 mg/dL,

          -  fasting C-peptide < 0.21 pmol/ml,

          -  Alanine Amino Transaminase (ALT) > 3 times normal or serum bilirubin > 1.9 mg/dL,

          -  malignancy or noncardiac life-threatening diseases making life expectancy < 5 years,

          -  autonomic neuropathy,

          -  symptomatic pancreatic insufficiency (endocrine or exocrine),

          -  recurrent seizures within the past year,

          -  hypopituitarism,

          -  pregnancy, lactation, or planning a pregnancy,

          -  active psychosis or substance abuse,

          -  lack of access to a person who can assist or be called in an emergency,

          -  underlying conditions that in the site PI's judgment may prevent adherence to
             protocol,

          -  current participation in another clinical trial