Inclusion Criteria

1. Type 2 diabetes mellitus defined according to the 1997 ADA criteria:

•   Fasting plasma glucose >126 mg/dl, or
•   Symptoms of hyperglycemia with casual plasma glucose >200 mg/dl, or
•   2-hour plasma glucose >200 mg/dl after a 75 gram oral glucose load

2. HbA1c:

• 7.5 to 11%

if on insulin <1 unit/kg plus on 0 or 1 oral agent, or

if not on insulin, on 0, 1, or 2 oral agents

• 7.5 to 9%

a)     if on insulin <1 unit/kg plus on 2 oral agents, or

b)     if not on insulin plus on 3 oral agents, or

c)     if on insulin >1 unit/kg plus 0 oral agents

Oral agents include: a) insulin secretagogues (sulfonylurea, meglitinides), b) biguanides c) insulin enhancers (thiazolidinediones)

The upper limits for HbA1c were selected to increase the likelihood of reaching the study’s HbA1c targets. The lower limit was selected to allow for further reduction should the participant be assigned to the intensive glycemic group.

3. Known diabetes duration >3 months

4. Stable diabetes therapy for >3 months (dose of any 1 antihyperglycemic drug has not changed by more than two-fold and new agents have not been added within the previous 3 months)

5. Age:

•   ≥40 years for anyone with a history of clinical cardiovascular disease (defined below in Item #6A), regardless of racial/ethnic group

•  ≥55 years for anyone without a history of clinical cardiovascular disease (defined below in Item #6A), regardless of racial/ethnic group

6. At high risk of cardiovascular events, defined as:

    A. Presence of clinical cardiovascular disease.

• previous myocardial infarction (MI)

• previous stroke

• history of coronary revascularization (e.g., coronary artery bypass graft surgery, stent placement, percutaneous transluminal coronary angioplasty, or laser atherectomy)

• history of carotid or peripheral revascularization (e.g., carotid endarterectomy, lower extremity atherosclerotic disease atherectomy, repair of abdominal aorta aneurysm, femoral or popliteal bypass)

• angina with ischemic changes (resting ECG), ischemic ECG changes during an exercise test, or positive cardiac imaging study

or

B. If no clinical cardiovascular disease, evidence in the last 2 years suggesting a high likelihood of cardiovascular disease. Specifically, the presence of one of the following:

• microalbuminuria

• ankle brachial index <0.9 (by simple palpation)

• LVH by ECG or echocardiogram

• >50% stenosis of a coronary, carotid, or lower extremity artery

or

C. The presence of at least 2 of the following factors that increase CVD risk:

• On lipid lowering medication or untreated LDL-C >130 mg/dl

• Low HDL-C (<40 mg/dl) for men and <50 mg/dl for women

• On BP lowering medication or untreated, SBP >140 mm Hg or DBP > 95 mm Hg.

• Current cigarette smoking

• Body mass index >32 kg/m ²

Note: Category A represents secondary prevention participants. Categories B and C together represent primary prevention participants.

Additional eligibility criteria for participants in the lipid component of ACCORD

Participants are eligible for the lipid component if the following criteria are met.

• 85 mg/dl < LDL-C < 170 mg/dl if not on a lipid-lowering agent

and

• HDL-C less than 50 mg/dl for all gender-race groups

and

• triglycerides <750 mg/dl on no therapy or <400 mg/dl on treatment with lipid lowering drugs

Additional eligibility criteria for participants in the blood pressure component of ACCORD