Mealtime glucose regulation with Nateglinide in healthy volunteers: comparison with repaglinide and placebo

• Published in: Diabetes care Vol. 24; no. 1; pp. 73 - 77
• Main Authors: KALBAG, Jyoti B, NEDELMAN, Jerry R, WALTER, Yulia H, MCLEOD, James F
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 2001
• Subjects: Adolescent; Adult; Associated diseases and complications; Biological and medical sciences; Blood Glucose - metabolism; Body Mass Index; Body Weight; Carbamates - pharmacology; Cross-Over Studies; Cyclohexanes - administration & dosage; Cyclohexanes - pharmacokinetics; Cyclohexanes - pharmacology; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Evaluation; Female; Food; General and cellular metabolism. Vitamins; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - pharmacokinetics; Hypoglycemic Agents - pharmacology; Insulin - blood; Insulin - metabolism; Insulin Secretion; Kinetics; Male; Medical sciences; Middle Aged; Nateglinide; Pharmacology. Drug treatments; Phenylalanine - administration & dosage; Phenylalanine - analogs & derivatives; Phenylalanine - pharmacokinetics; Phenylalanine - pharmacology; Piperidines - pharmacology; Placebos; Product/service Evaluations; Repaglinide; Time Factors; United States; Human; Participation; Healthy subject; Secretion; Single dose; Label; Glucose; Hypoglycemia; Crossover study; Insulin; Regulation(control); Repaglinide; Pharmacokinetics; Comparative study
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.24.1.73

This study was designed to compare the pharmacodynamic effects of single doses of nateglinide (A-4166), repaglinide, and placebo on mealtime insulin secretion and glycemic control in healthy subjects. Fifteen healthy volunteers participated in this open-label five-period crossover study. They received single 10-min preprandial doses of 120 mg nateglinide, 0.5 or 2 mg repaglinide, or placebo or 1 min preprandially of 2 mg repaglinide. Subjects received each dose only once, 48 h apart. Pharmacodynamic and pharmacokinetic assessments were performed from 0 to 12 h postdose. Nateglinide induced insulin secretion more rapidly than 2 and 0.5 mg repaglinide and placebo (10 min preprandial), with mean rates of insulin rise of 2.3, 1.3, 1.15, and 0.8 microU x ml(-1) x min(-1), respectively, over the 0- to 30-min postmeal interval. After peaking, insulin concentrations decreased rapidly in the nateglinide-treated group and were similar to placebo within 2 h postdose. After 2 mg repaglinide, peak insulin concentrations were delayed and returned to baseline more slowly than with nateglinide treatment. Nateglinide treatment produced lower average plasma glucose concentrations in the 0- to 2-h postdose interval than either dose of repaglinide and placebo (P < 0.05 vs. 0.5 mg repaglinide and placebo). Plasma glucose concentrations returned more rapidly to predose levels with nateglinide treatment than with either dose of repaglinide. Treatment with repaglinide produced a sustained hypoglycemic effect up to 6 h postdose. In this single-dose study in nondiabetic volunteers, nateglinide provided a more rapid and shorter-lived stimulation of insulin secretion than repaglinide, resulting in lower meal-related glucose excursions. If similar results are observed in diabetes, nateglinide may produce a more physiological insulin secretory response with the potential for a reduced risk of postabsorptive hypoglycemia.