Randomized Dose Ranging Study of the Reduction of Fasting and Postprandial Glucose in Type 2 Diabetes by

OBJECTIVE — This randomized crossover double-blind placebo-controlled study aimed to assess the efficacy of nateglinide (A-4166), a novel phenylalanine-derived insulin secretagogue, in type 2 diabetic subjects while fasting and 5 min before a standard meal. RESEARCHDESIGNANDMETHODS — A single dose of nateglinide (60, 120, or 180 mg) or placebo was given to eight diet-treated overnight-fasted type 2 diabetic patients and to seven patients 5 min before a standard breakfast. Plasma glucose, radioimmunoassay insulin, and nateglinide were measured at baseline and for a further 180 min. RESULTS — The time-averaged 180-min postdose mean decrease in fasting plasma glucose concentration was greater after nateglinide (1.8 mmol/l; 95 % CI 1.5–2.0) than after placebo (0.7 mmol/l; 95 % CI 0.3–1.2) (P, 0.001). Hypoglycemia did not develop in any of the subjects. Insulin concentrations increased 1.5-, 1.8-, and 1.9-fold with the 60-, 120-, and 180-mg doses, respectively (P, 0.001), peaking;30 min after the dose. Nateglinide concentrations peaked after;30 min, decreasing to 21 % of peak by 180 min. In the meal test, the mean increase (2.9 mmol/l, 2.3–3.6) in plasma glucose over 180 min after placebo was reduced by 1.8 mmol/l (P, 0.001) with the two higher doses of nateglinide