Study of the Durability of Glycemic Control With Nateglinide

Selected patients will be randomly assigned to receive nateglinide or glimepiride.

Previous treatment with oral antidiabetic drugs (metformin, a-glucosidase inhibitor, nateglinide or sulfonylurea) will be discontinued. After a 1 month wash-out period (if 6.5 ≤ HbA1c ≤ 8.5), patients will take randomly assigned drugs for 24 months.

Patients will be met by the trial investigator every 3 months following randomization. At each visit, patients whose HbA1c is > 8.0% will be retested 2 weeks later, and if the retested HbA1c is also above 8.0%, those patients will be withdrawn considering monotherapy failure. We will evaluate the durability of nateglinide in comparison with that of glimepiride based on the withdrawal rate.

Inclusion criteria

• type 2 diabetes mellitus
• age>=18years
• no anti hyperglycemic agent for 3 months or low-dose oral hypoglycemic therapy

• metformin≤1g/day, acarbose≤300mg/day, voglibose≤0.9mg/day, nateglinide≤270mg/day, gliclazide≤80mg/day, glimepiride≤2mg/day, glibenclamide≤5mg/day (nateglinide or sulfonylurea <6months)
• 6.5% ≤ HbA1c ≤ 8.5%

• patients on no anti hyperglycemic agent for 3 months : HbA1c at screening
• patients on oral hypoglycemic therapy in 3months : HbA1c after wash-out

Exclusion criteria

• attending other clinical trials in 3months
• type I diabetes mellitus
• taking systemic steroid in 1month or requiring steroid therapy during clinical trial
• acute myocardial infarction in 6months
• alcoholics, pituitary or adrenal insufficiency, severe ketosis, diabetic ketoacidosis
• severe liver disease or AST, ALT ≥ 2.5 x ULN
• renal insufficiency (serum creatinine > 2.0mg/dl)
• other severe diabetic complication
• drug hypersensitivity history to nateglinide or sulfonylurea
• pregnant or plan to become pregnant during the clinical trial, lactation