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Chemical Compound Review

Starlix     (2S)-3-phenyl-2-[(4-propan- 2...

Synonyms: Starsis, Fastic, IPCCPA, Trazec, senaglinide, ...
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Disease relevance of nateglinide


High impact information on nateglinide


Chemical compound and disease context of nateglinide


Biological context of nateglinide


Anatomical context of nateglinide


Associations of nateglinide with other chemical compounds

  • Plasma glucose, radioimmunoassay insulin, and nateglinide were measured at baseline and for a further 180 min [10].
  • RESEARCH DESIGN AND METHODS--This randomized, double-blind, placebo-controlled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n = 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n = 50), or placebo (n = 51) for 8 weeks [17].
  • RESEARCH DESIGN AND METHODS: In this randomized double-blind study, patients with an HbA1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172) [23].
  • The area under the curve for the glucose excursion above baseline was also higher with placebo (14.1 +/- 1.8 mmol/h. l) compared with glipizide (6.9 +/- 2.4 mmol/h. l, P = 0.002), nateglinide (9.7 +/- 2 mmol/h. l, P = 0.004), or glipizide plus nateglinide (5.6 +/- 2.2 mmol/h. l, P < 0.001) [12].
  • The peak plasma concentration of the M7 metabolite of nateglinide was reduced by 34% by fluconazole (P <.001), and its half-life was prolonged from 2.2 to 3.5 hours (P <.05) [15].

Gene context of nateglinide


Analytical, diagnostic and therapeutic context of nateglinide

  • Repaglinide versus nateglinide monotherapy: a randomized, multicenter study [5].
  • Mild hypoglycaemia was the most frequently reported adverse event (1.3% of patients) after treatment with nateglinide 120 mg 3 times daily in a 16-week clinical study [28].
  • METHODS: A double-blind, placebo-controlled trial, examining the effects of a single oral dose of 60 mg nateglinide, given 20 min prior to an intravenous glucose tolerance test (IGTT), on insulin secretion in 10 otherwise healthy Caucasian men with recently diagnosed Type 2 diabetes (duration since diagnosis 0-44 months) [29].
  • Twelve healthy male subjects completed this randomized, single-dose, four-way crossover study in which each subject received a 60 mg dose of nateglinide 10 minutes before the start of and immediately after a high-fat breakfast meal [30].
  • Serial plasma samples were collected for 24 h postdose and analyzed for SDZ DJN 608 using HPLC [31].


  1. Oral antihyperglycemic agents and renal disease: new agents, new concepts. Yale, J.F. J. Am. Soc. Nephrol. (2005) [Pubmed]
  2. Nateglinide improves early insulin secretion and controls postprandial glucose excursions in a prediabetic population. Saloranta, C., Guitard, C., Pecher, E., De Pablos-Velasco, P., Lahti, K., Brunel, P., Groop, L. Diabetes Care (2002) [Pubmed]
  3. Synergistic effects of nateglinide and meal administration on insulin secretion in patients with type 2 diabetes mellitus. Keilson, L., Mather, S., Walter, Y.H., Subramanian, S., McLeod, J.F. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  4. Hypoglycemia following a nateglinide overdose in a suicide attempt. Nakayama, S., Hirose, T., Watada, H., Tanaka, Y., Kawamori, R. Diabetes Care (2005) [Pubmed]
  5. Repaglinide versus nateglinide monotherapy: a randomized, multicenter study. Rosenstock, J., Hassman, D.R., Madder, R.D., Brazinsky, S.A., Farrell, J., Khutoryansky, N., Hale, P.M. Diabetes Care (2004) [Pubmed]
  6. Differential interactions of nateglinide and repaglinide on the human beta-cell sulphonylurea receptor 1. Hansen, A.M., Christensen, I.T., Hansen, J.B., Carr, R.D., Ashcroft, F.M., Wahl, P. Diabetes (2002) [Pubmed]
  7. Pharmacologic restoration of the early insulin response in pre-diabetic monkeys controls mealtime glucose excursions without peripheral hyperinsulinaemia. Dunning, B.E., Deacon, R., Gutierrez, C., Paladini, S., Valentin, M.A., Foley, J.E. Diabetologia (2003) [Pubmed]
  8. Improved prandial glucose control with lower risk of hypoglycemia with nateglinide than with glibenclamide in patients with maturity-onset diabetes of the young type 3. Tuomi, T., Honkanen, E.H., Isomaa, B., Sarelin, L., Groop, L.C. Diabetes Care (2006) [Pubmed]
  9. Beta-cell function in mild type 2 diabetic patients: effects of 6-month glucose lowering with nateglinide. Mari, A., Gastaldelli, A., Foley, J.E., Pratley, R.E., Ferrannini, E. Diabetes Care (2005) [Pubmed]
  10. Randomized dose ranging study of the reduction of fasting and postprandial glucose in type 2 diabetes by nateglinide (A-4166). Gribble, F.M., Manley, S.E., Levy, J.C. Diabetes Care (2001) [Pubmed]
  11. Treatment of patients over 64 years of age with type 2 diabetes: experience from nateglinide pooled database retrospective analysis. Del Prato, S., Heine, R.J., Keilson, L., Guitard, C., Shen, S.G., Emmons, R.P. Diabetes Care (2003) [Pubmed]
  12. Control of postprandial hyperglycemia: optimal use of short-acting insulin secretagogues. Carroll, M.F., Izard, A., Riboni, K., Burge, M.R., Schade, D.S. Diabetes Care (2002) [Pubmed]
  13. Addition of nateglinide to rosiglitazone monotherapy suppresses mealtime hyperglycemia and improves overall glycemic control. Fonseca, V., Grunberger, G., Gupta, S., Shen, S., Foley, J.E. Diabetes Care (2003) [Pubmed]
  14. Effects of the Combination of a Dipeptidyl Peptidase IV Inhibitor and an Insulin Secretagogue on Glucose and Insulin Levels in Mice and Rats. Yamazaki, K., Yasuda, N., Inoue, T., Yamamoto, E., Sugaya, Y., Nagakura, T., Shinoda, M., Clark, R., Saeki, T., Tanaka, I. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  15. Effect of fluconazole on the pharmacokinetics and pharmacodynamics of nateglinide. Niemi, M., Neuvonen, M., Juntti-Patinen, L., Backman, J.T., Neuvonen, P.J. Clin. Pharmacol. Ther. (2003) [Pubmed]
  16. In type 2 diabetes, rosiglitazone therapy for insulin resistance ameliorates endothelial dysfunction independent of glucose control. Pistrosch, F., Passauer, J., Fischer, S., Fuecker, K., Hanefeld, M., Gross, P. Diabetes Care (2004) [Pubmed]
  17. Importance of early insulin secretion: comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes. Hollander, P.A., Schwartz, S.L., Gatlin, M.R., Haas, S.J., Zheng, H., Foley, J.E., Dunning, B.E. Diabetes Care (2001) [Pubmed]
  18. Sulfonylurea induced beta-cell apoptosis in cultured human islets. Maedler, K., Carr, R.D., Bosco, D., Zuellig, R.A., Berney, T., Donath, M.Y. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  19. Clinical pharmacokinetics of nateglinide: a rapidly-absorbed, short-acting insulinotropic agent. McLeod, J.F. Clinical pharmacokinetics. (2004) [Pubmed]
  20. A novel D-phenylalanine-derivative hypoglycemic agent A-4166 increases cytosolic free Ca2+ in rat pancreatic beta-cells by stimulating Ca2+ influx. Fujitani, S., Yada, T. Endocrinology (1994) [Pubmed]
  21. Transport and uptake of nateglinide in Caco-2 cells and its inhibitory effect on human monocarboxylate transporter MCT1. Okamura, A., Emoto, A., Koyabu, N., Ohtani, H., Sawada, Y. Br. J. Pharmacol. (2002) [Pubmed]
  22. H+-dependent transport mechanism of nateglinide in the brush-border membrane of the rat intestine. Itagaki, S., Saito, Y., Kubo, S., Otsuka, Y., Yamamoto, Y., Kobayashi, M., Hirano, T., Iseki, K. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  23. Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes. Horton, E.S., Clinkingbeard, C., Gatlin, M., Foley, J., Mallows, S., Shen, S. Diabetes Care (2000) [Pubmed]
  24. Influence of CYP2C9 and CYP2D6 polymorphisms on the pharmacokinetics of nateglinide in genotyped healthy volunteers. Kirchheiner, J., Meineke, I., Müller, G., Bauer, S., Rohde, W., Meisel, C., Roots, I., Brockmöller, J. Clinical pharmacokinetics. (2004) [Pubmed]
  25. Coadministration of gemfibrozil and itraconazole has only a minor effect on the pharmacokinetics of the CYP2C9 and CYP3A4 substrate nateglinide. Niemi, M., Backman, J.T., Juntti-Patinen, L., Neuvonen, M., Neuvonen, P.J. British journal of clinical pharmacology. (2005) [Pubmed]
  26. Nateglinide, a D-phenylalanine derivative lacking either a sulfonylurea or benzamido moiety, specifically inhibits pancreatic beta-cell-type K(ATP) channels. Chachin, M., Yamada, M., Fujita, A., Matsuoka, T., Matsushita, K., Kurachi, Y. J. Pharmacol. Exp. Ther. (2003) [Pubmed]
  27. Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2. Terada, T., Sawada, K., Saito, H., Hashimoto, Y., Inui, K. Eur. J. Pharmacol. (2000) [Pubmed]
  28. Nateglinide. Dunn, C.J., Faulds, D. Drugs (2000) [Pubmed]
  29. Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in Type 2 diabetes mellitus. Whitelaw, D.C., Clark, P.M., Smith, J.M., Nattrass, M. Diabet. Med. (2000) [Pubmed]
  30. The effect of food on the oral bioavailability and the pharmacodynamic actions of the insulinotropic agent nateglinide in healthy subjects. Karara, A.H., Dunning, B.E., McLeod, J.F. Journal of clinical pharmacology. (1999) [Pubmed]
  31. Effect of food on the bioavailability of SDZ DJN 608, an oral hypoglycemic agent, from a tablet and a liquid-filled capsule in the dog. Tse, F.L., Labbadia, D., Habucky, K., Karara, A., Au, S. Pharm. Res. (1996) [Pubmed]
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