Table 1

Inclusion/Exclusion Criteria.

• 1. Inclusion Criteria

• Men and women

• All ethnic groups

• ≥ 18 years of age

• IGT with a FPG = 95–125 mg/dl plus at least one additional high risk

• characteristic (see text). IGT is defined as a two hour plasma glucose

• concentration = 140–199 mg/dl during a single 75 gram OGTT.

• BMI ≥ 25 kg/m² (no upper limit) (BMI > 22 kg/m² for Asian Americans)

1. Exclusion Criteria

• Subjects with diabetes mellitus: FPG ≥ 126 mg/dl or 2-hour plasma glucose ≥ 200 mg/dl during OGTT.

• Subjects previously treated with a thiazolidinedione (ever) or metformin (within one year prior to randomization)

• Subjects previously treated with a sulfonylurea, a meglitinide, an alpha glucosidase inhibitor for more than one week within the last year, or within the 3 months prior to randomization

• Subjects previously treated with insulin (other than during pregnancy) for more than one week within the last year or within the 3 months prior randomization.

• Medical conditions likely to limit life span and/or increase risk of intervention

- Cardiovascular disease

- Hospitalization for treatment of heart disease or stroke in past 6 months

- New York Heart Association Functional Class > 2

- Left bundle branch block or third degree AV block

- Aortic stenosis

- Systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg; subjects can be re-screened after treatment of their hypertension

- Renal disease (creatine ≥ 1.6 mg/dl for men or ≥ 1.5 mg/dl for women, or urine protein ≥ 2+)

- Anemia (hematocrit < 33% in men and < 30% in women); if the hematocrit increases above these levels at a later date, they can be included in the study

• Hepatitis, based on history and/or serum ALT greater than 2.5 times the upper limit of normal

- Other gastrointestinal disease (pancreatitis, inflammatory bowel disease)

- Recent or significant abdominal surgery

- Pulmonary disease with dependence on oxygen or daily use of bronchodilators

- Chronic infection (e.g., HIV, active tuberculosis)

• Conditions or behaviors likely to affect conduct of the trial

- Unwilling to accept treatment assignment by randomization

- Participation in another intervention research project that might interfere with completion of the study

- Weight loss of > 10% in past 6 months for any reason except postpartum weight loss

- Currently pregnant or within 3 months postpartum

- Currently nursing or within 6 weeks of having completed nursing

- Pregnancy anticipated during the course of the trial

- Unwilling to undergo pregnancy testing or report possible pregnancy promptly

- Unwilling to take precautions to avoid pregnancy if potentially fertile

• Major psychiatric disorders

• Excessive alcohol intake, either acute or chronic

• Medications and medical conditions likely to confound the assessment for diabetes, including:

Thiazide diuretics at a dose greater than 25 mg/day

Non-cardioselective beta-blockers (individuals receiving treatment with a statin or fenofibrate will not be excluded as long as the dose has been stable for 3 months prior to randomization)

Glucocorticoids, systemic

Prescription weight-loss or weight-gain medications

• Thyroid disease, suboptimally treated as indicated by abnormal serum thyroid-stimulating hormone

• Other endocrine disorders (e.g. Cushing's syndrome, acromegaly)

• Fasting plasma triglyceride > 400 mg/dl, despite treatment

• Individuals with a history of bladder cancer

• Individuals with hematuria at screening. However, subjects with hematuria may be randomized if the cause of the hematuria is found, treated, and thought unlikely to recur.

DeFronzo et al. BMC Endocrine Disorders 2009 9:17   doi:10.1186/1472-6823-9-17