Mealtime glucose regulation by nateglinide in type-2 diabetes mellitus

Objectives: Pharmacodynamic effects of nateglinide, a novel antidiabetic ag ent, were investigated in patients with type-2 diabetes mellitus. Methods: Ten patients participated in this single-center, double-blind, cro ssover study. Plasma glucose and insulin levels were measured over 24 h fol lowing five 7-day treatment periods with nateglinide (30, 60, or 120 mg) or placebo given three times daily before breakfast, lunch, and dinner. A fif th treatment consisted of 120 mg nateglinide four times daily, with the fou rth dose given before an evening snack. Results: Taken 10 min before meals, doses of 30-120 mg nateglinide caused d ose-dependent increases in plasma insulin levels that were significantly gr eater than with placebo. Higher doses were more effective and had a longer duration of action than lower doses. Nateglinide was also significantly bet ter than placebo in lowering plasma glucose levels; the 60-mg and 120-mg do ses were similarly effective and superior to the 30-mg nateglinide treatmen t. Following the fourth 120-mg dose, the glucose-lowering effects of treatm ent were maintained through the night. No serious adverse events occurred d uring the study. There were no events of hypoglycemia and no clinically mea ningful changes in safety parameters. Conclusions: Nateglinide produced rapid, short-lived, dose-related increase s in plasma insulin that significantly lowered mealtime glucose excursions compared with placebo with no incidence of hypoglycemia. The decrease in me altime glucose levels produced a significant improvement in overall 24-h gl ycemia.