This multi-center, randomized controlled study aims to evaluate the durability and efficacy of nateglinide therapy for long term glycemic control compared with glimepiride.

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 8.0% will be retested 2 weeks later, and if the retested HbA1c is also above 8.0%, those patients will be withdrawn considering monotherapy failure.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

6 months