Nateglinide provides tighter glycaemic control than glyburide in patients with Type 2 diabetes with prevalent postprandial hyperglycaemia

Postprandial hyperglycaemia in patients with Type 2 diabetes mellitus has been linked to the development of cardiovascular disease. This study compared the effects of mealtime (thrice-daily) nateglinide with once-daily glyburide on postprandial glucose levels in patients with Type 2 diabetes and postprandial hyperglycaemia.

Patients with Type 2 diabetes aged ≥ 21 years with 2-h postprandial glucose levels ≥ 11.1 mmol/l, HbA(1c) of 6.5-8.5% (48-69 mmol/mol) and BMI of 22-30 kg/m(2) were randomized to 6 weeks' double-blind treatment with nateglinide 120 mg three times daily prior to meals, or glyburide 5 mg once daily before breakfast. The primary endpoint was the baseline-adjusted change in plasma glucose from preprandial (fasting plasma glucose) to 2-h postprandial glucose levels (2-h postprandial glucose excursion) at 6 weeks.

Patients were randomized to nateglinide (n = 122) or glyburide (n = 110). The treatment groups were similar in terms of age, gender, BMI, fasting plasma glucose, 2-h postprandial glucose and HbA(1c). At endpoint, nateglinide recipients had significantly greater reductions than those receiving glyburide in both the 2-h (-2.4 vs. -1.6 mmol/l; P = 0.02) and 1-h (-1.7 vs. -0.9 mmol/l; P = 0.016) postprandial glucose excursions. Adverse events, most commonly symptomatic hypoglycaemia, were reported in 26% of recipients of glyburide and 22% of recipients of nateglinide. Episodes of suspected mild hypoglycaemia were reported in 24% of recipients of glyburide and 10% of recipients of nateglinide.

Nateglinide leads to greater reductions in postprandial glucose excursions and is associated with a lower risk of hypoglycaemia than glyburide in this selected population of patients with Type 2 diabetes.