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

Diabet. Med. 28, 560–566 (2011) Abstract Aims  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. Methods  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. Results  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. Conclusions  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.