Skip to main content
Erschienen in: Drugs 3/2000

01.09.2000 | Adis New Drug Profile

Nateglinide

verfasst von: Christopher J. Dunn, Diana Faulds

Erschienen in: Drugs | Ausgabe 3/2000

Einloggen, um Zugang zu erhalten

Abstract

▴ Nateglinide is a novel D-phenylalanine derivative that inhibits ATP-sensitive K+ channels in pancreatic β-cells in the presence of glucose and thereby stimulates the prandial release of insulin.
▴ Nateglinide reduces fasting and mealtime blood glucose levels in animals, healthy volunteers, and patients with type 2 (non-insulin-dependent) diabetes mellitus, and produces prompt prandial insulin responses with return to baseline insulin levels between meals.
▴ In randomised, double-blind 24-week studies in patients with type 2 diabetes, oral nateglinide 120mg 3 times daily before meals improved glycaemic control significantly relative to placebo.
▴ Nateglinide 120mg plus metformin 500mg, both 3 times daily, conferred greater glycaemic improvement than either drug given alone, and nateglinide 60 or 120mg 3 times daily plus metformin 1g twice daily was superior to metformin plus placebo.
▴ Nateglinide 120mg 3 times daily significantly reduced hyperglycaemia relative to placebo in a 16-week double-blind study in patients with type 2 diabetes mellitus. Combination therapy with troglitazone 600mg daily produced significantly better glycaemic control than either drug given as monotherapy.
▴ Mild hypoglycaemia was the most frequently reported adverse event (1.3% of patients) after treatment with nateglinide 120mg 3 times daily in a 16-week clinical study. No clinically significant abnormalities in laboratory results, ECGs, vital signs or physical examination findings have been noted in patients taking the drug.
Literatur
1.
Zurück zum Zitat Perfetti R, Mathur R, Egan JM. New insulin secretagogues for the treatment of type 2 diabetes. Dis Manage Clin Outcomes 1998 Jul–Aug; 1: 129–35CrossRef Perfetti R, Mathur R, Egan JM. New insulin secretagogues for the treatment of type 2 diabetes. Dis Manage Clin Outcomes 1998 Jul–Aug; 1: 129–35CrossRef
2.
Zurück zum Zitat Fujitani S, Yada T. A novel D-phenylalanine-derivative hypoglycemic agent A-4166 increases cytosolic free Ca2+ in rat pancreatic β-cells by stimulating Ca2+ influx. Endocrinology 1994 Mar; 134: 1395–400PubMedCrossRef Fujitani S, Yada T. A novel D-phenylalanine-derivative hypoglycemic agent A-4166 increases cytosolic free Ca2+ in rat pancreatic β-cells by stimulating Ca2+ influx. Endocrinology 1994 Mar; 134: 1395–400PubMedCrossRef
3.
Zurück zum Zitat Hu S, Wang S, Dunning BE. Tissue selectivity of nateglinide: study on cardiovascular and β-cell Katp channels [abstract]. Diabetes 1999 May; 48 Suppl. 1: A249 Hu S, Wang S, Dunning BE. Tissue selectivity of nateglinide: study on cardiovascular and β-cell Katp channels [abstract]. Diabetes 1999 May; 48 Suppl. 1: A249
4.
Zurück zum Zitat Hu S, Wang S, Fanelli F, et al. Pancreatic β-cell Katpchannel activity and membrane-binding studies with nateglinide: a comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther 2000; 293(2): 444–52PubMed Hu S, Wang S, Fanelli F, et al. Pancreatic β-cell Katpchannel activity and membrane-binding studies with nateglinide: a comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther 2000; 293(2): 444–52PubMed
5.
Zurück zum Zitat Fujitani S, Ikenoue T, Akiyoshi M, et al. Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreas. Metabolism 1996 Feb;45: 184–9PubMedCrossRef Fujitani S, Ikenoue T, Akiyoshi M, et al. Somatostatin and insulin secretion due to common mechanisms by a new hypoglycemic agent, A-4166, in perfused rat pancreas. Metabolism 1996 Feb;45: 184–9PubMedCrossRef
6.
Zurück zum Zitat Malaisse WJ. Insulinotropic action of meglitinide analogues: modulation by an activator of ATP-sensitive K+ channels and high extracellular K+concentrations. Pharmacol Res 1995; 32(3): 111–4PubMedCrossRef Malaisse WJ. Insulinotropic action of meglitinide analogues: modulation by an activator of ATP-sensitive K+ channels and high extracellular K+concentrations. Pharmacol Res 1995; 32(3): 111–4PubMedCrossRef
7.
Zurück zum Zitat Bokvist K, Høy M, Poulsen CR, et al. A4166, but not repaglinide, stimulate Ca2+-evoked, KATpchannel independent, secretion in rat pancreatic (X- and β-cells [abstract]. Diabetologia 1998 Aug; 41 Suppl. 1: A139 Bokvist K, Høy M, Poulsen CR, et al. A4166, but not repaglinide, stimulate Ca2+-evoked, KATpchannel independent, secretion in rat pancreatic (X- and β-cells [abstract]. Diabetologia 1998 Aug; 41 Suppl. 1: A139
8.
Zurück zum Zitat Fujita T, Seto Y, Kondo N, et al. Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) receptor in HIT T-15 cells. Displacement of [3H]glibenclamide. Biochem Pharmacol 1996; 52: 407–11CrossRef Fujita T, Seto Y, Kondo N, et al. Studies on the N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) receptor in HIT T-15 cells. Displacement of [3H]glibenclamide. Biochem Pharmacol 1996; 52: 407–11CrossRef
9.
Zurück zum Zitat Hu S, Wang S. Effect of antidiabetic agent, nateglinide, on Katp channel in β-cells: comparison to glyburide and repaglinide [abstract]. Diabetologia 1998 Aug; 41 Suppl. 1: A139 Hu S, Wang S. Effect of antidiabetic agent, nateglinide, on Katp channel in β-cells: comparison to glyburide and repaglinide [abstract]. Diabetologia 1998 Aug; 41 Suppl. 1: A139
10.
Zurück zum Zitat Akiyoshi M, Kakei M, Nakazaki M. A new hypoglycemic agent, A-4166, inhibits ATP-sensitive potassium channels in rat pancreatic β-cells. Am J Physiol 1995; 268 (2 Pt 1): E185–93PubMed Akiyoshi M, Kakei M, Nakazaki M. A new hypoglycemic agent, A-4166, inhibits ATP-sensitive potassium channels in rat pancreatic β-cells. Am J Physiol 1995; 268 (2 Pt 1): E185–93PubMed
11.
Zurück zum Zitat Ikenoue T, Akiyoshi M, Fujitani S, et al. Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166). Br J Pharmacol 1997; 120: 137–45PubMedCrossRef Ikenoue T, Akiyoshi M, Fujitani S, et al. Hypoglycaemic and insulinotropic effects of a novel oral antidiabetic agent, (-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine (A-4166). Br J Pharmacol 1997; 120: 137–45PubMedCrossRef
12.
Zurück zum Zitat Ikenoue T, Okazaki K, Fujitani S, et al. Effect of a new hypoglycemie agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide. Biol Pharm Bull 1997; 20(4): 354–9PubMedCrossRef Ikenoue T, Okazaki K, Fujitani S, et al. Effect of a new hypoglycemie agent, A-4166 [(-)-N-(trans-4-isopropylcyclohexanecarbonyl)-D-phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide. Biol Pharm Bull 1997; 20(4): 354–9PubMedCrossRef
13.
Zurück zum Zitat Morimoto S, Mokuda O, Sakamoto Y. AY-4166 increases the sensitivity of insulin secretion to glucose in isolated perfused rat pancreas. Horm Metab Res 1998 Feb; 30: 77–9PubMedCrossRef Morimoto S, Mokuda O, Sakamoto Y. AY-4166 increases the sensitivity of insulin secretion to glucose in isolated perfused rat pancreas. Horm Metab Res 1998 Feb; 30: 77–9PubMedCrossRef
14.
Zurück zum Zitat Leclercqmeyer V, Ladriere L, Fuhlendorff J, et al. Stimulation of insulin and somatostatin release by two meglitinide analogs. Endocrine 1997 Dec; 7: 311–7CrossRef Leclercqmeyer V, Ladriere L, Fuhlendorff J, et al. Stimulation of insulin and somatostatin release by two meglitinide analogs. Endocrine 1997 Dec; 7: 311–7CrossRef
15.
Zurück zum Zitat Hirose H, Maruyama H, Ito K, et al. Effects of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas. Pharmacology 1994 Apr; 48: 205–10PubMedCrossRef Hirose H, Maruyama H, Ito K, et al. Effects of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine (A-4166) on insulin and glucagon secretion in isolated perfused rat pancreas. Pharmacology 1994 Apr; 48: 205–10PubMedCrossRef
16.
Zurück zum Zitat Whitelaw DC, Collins J, Smith S, et al. The new oral hypoglycaemic agent A4166 enhances 1st phase insulin secretion in diabetic man [abstract]. Diabetic Med 1995; 12 Suppl. 2: S37 Whitelaw DC, Collins J, Smith S, et al. The new oral hypoglycaemic agent A4166 enhances 1st phase insulin secretion in diabetic man [abstract]. Diabetic Med 1995; 12 Suppl. 2: S37
17.
Zurück zum Zitat Kalbag J, Hirschberg Y, McLeod JF, et al. Comparison of mealtime glucose regulation by nateglinide and repaglinide in healthy subjects [abstract]. Diabetes 1999 May; 48 Suppl. 1: A106CrossRef Kalbag J, Hirschberg Y, McLeod JF, et al. Comparison of mealtime glucose regulation by nateglinide and repaglinide in healthy subjects [abstract]. Diabetes 1999 May; 48 Suppl. 1: A106CrossRef
18.
Zurück zum Zitat Hirschberg Y, McLeod J, Garreffa S, et al. Pharmacodynamics and dose response of nateglinide in type 2 diabetics [abstract]. Diabetes 1999 May; 48 Suppl. 1: A100 Hirschberg Y, McLeod J, Garreffa S, et al. Pharmacodynamics and dose response of nateglinide in type 2 diabetics [abstract]. Diabetes 1999 May; 48 Suppl. 1: A100
19.
Zurück zum Zitat Hollander P, Schwartz S, Gatlin M, et al. Nateglinide, but not glyburide, selectively enhances early insulin release and more effectively controls post-meal glucose excursions with less total insulin exposure [abstract]. Diabetes 2000 May; 49 Suppl. 1: A111 Hollander P, Schwartz S, Gatlin M, et al. Nateglinide, but not glyburide, selectively enhances early insulin release and more effectively controls post-meal glucose excursions with less total insulin exposure [abstract]. Diabetes 2000 May; 49 Suppl. 1: A111
20.
Zurück zum Zitat Horton E, Clinkingbeard C, Gatlin M, et al. Nateglinide alone and in combination with metformin improves glycemie control by reducing mealtime glucose spikes in type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A112 Horton E, Clinkingbeard C, Gatlin M, et al. Nateglinide alone and in combination with metformin improves glycemie control by reducing mealtime glucose spikes in type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A112
21.
Zurück zum Zitat Hirschberg Y, Karara AH, Pietri AO, et al. Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin. Diabetes Care 2000 Mar; 23(3): 349–53PubMedCrossRef Hirschberg Y, Karara AH, Pietri AO, et al. Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin. Diabetes Care 2000 Mar; 23(3): 349–53PubMedCrossRef
22.
Zurück zum Zitat Keilson L, Mather S, Walter YH, et al. Synergistic effects of nateglinide and meal administration on insulin secretion in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2000; 85(3): 1081–6PubMedCrossRef Keilson L, Mather S, Walter YH, et al. Synergistic effects of nateglinide and meal administration on insulin secretion in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2000; 85(3): 1081–6PubMedCrossRef
23.
Zurück zum Zitat Karara AH, Dunning BE, McLeod JF. The effect of food on the oral bioavailability and the pharmacodynamic actions of the insulinotropic actions of the agent nateglinide in healthy subjects. J Clin Pharmacol 1999 Feb; 39: 172–9PubMedCrossRef Karara AH, Dunning BE, McLeod JF. The effect of food on the oral bioavailability and the pharmacodynamic actions of the insulinotropic actions of the agent nateglinide in healthy subjects. J Clin Pharmacol 1999 Feb; 39: 172–9PubMedCrossRef
24.
Zurück zum Zitat Choudhury S, Hirschberg Y, Filipek R, et al. Single-dose pharmacokinetics of nateglinide in subjects with hepatic cirrhosis. J Clin Pharmacol 2000 Jun; 40(6): 634–40PubMedCrossRef Choudhury S, Hirschberg Y, Filipek R, et al. Single-dose pharmacokinetics of nateglinide in subjects with hepatic cirrhosis. J Clin Pharmacol 2000 Jun; 40(6): 634–40PubMedCrossRef
25.
Zurück zum Zitat Kikuchi M. Modulation of insulin secretion in non-insulin-dependent diabetes mellitus by two novel oral hypoglycaemic agents, NN623 and A4166. Diabetic Med 1996; 13 Suppl. 6: S151–5PubMed Kikuchi M. Modulation of insulin secretion in non-insulin-dependent diabetes mellitus by two novel oral hypoglycaemic agents, NN623 and A4166. Diabetic Med 1996; 13 Suppl. 6: S151–5PubMed
26.
Zurück zum Zitat Takesada H, Matsuda K, Ohtake R, et al. Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel D-phenylalanine-derivative hypoglycemie agent [published erratum appears in Bioorg Med Chem 1997 Mar; 5 (3): 637]. Bioorg Med Chem 1996 Oct; 4: 1771–81PubMedCrossRef Takesada H, Matsuda K, Ohtake R, et al. Structure determination of metabolites isolated from urine and bile after administration of AY4166, a novel D-phenylalanine-derivative hypoglycemie agent [published erratum appears in Bioorg Med Chem 1997 Mar; 5 (3): 637]. Bioorg Med Chem 1996 Oct; 4: 1771–81PubMedCrossRef
27.
Zurück zum Zitat Zhou H, Walter YH, Smith H, et al. Nateglinide, a new mealtime glucose regulator: lack of pharmacokinetic interaction with digoxin in healthy volunteers. Clin Drug Invest 2000 Jun; 19: 465–71CrossRef Zhou H, Walter YH, Smith H, et al. Nateglinide, a new mealtime glucose regulator: lack of pharmacokinetic interaction with digoxin in healthy volunteers. Clin Drug Invest 2000 Jun; 19: 465–71CrossRef
28.
Zurück zum Zitat Rosenstock J, Gatlin M, Mallows S, et al. Nateglinide improves glycemie control alone and in combination with troglitazone in patients with type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A123 Rosenstock J, Gatlin M, Mallows S, et al. Nateglinide improves glycemie control alone and in combination with troglitazone in patients with type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A123
29.
Zurück zum Zitat Marre M, Whatmough I, Pongowski M, et al. Nateglinide added to metformin offers safe and effective treatment for type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A361 Marre M, Whatmough I, Pongowski M, et al. Nateglinide added to metformin offers safe and effective treatment for type 2 diabetes [abstract]. Diabetes 2000 May; 49 Suppl. 1: A361
30.
Zurück zum Zitat Hanefeld M, Bouter KP, Dickinson S, et al. Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia. Diabetes Care 2000 Feb; 23(2): 202–7PubMedCrossRef Hanefeld M, Bouter KP, Dickinson S, et al. Rapid and short-acting mealtime insulin secretion with nateglinide controls both prandial and mean glycemia. Diabetes Care 2000 Feb; 23(2): 202–7PubMedCrossRef
Metadaten
Titel
Nateglinide
verfasst von
Christopher J. Dunn
Diana Faulds
Publikationsdatum
01.09.2000
Verlag
Springer International Publishing
Erschienen in
Drugs / Ausgabe 3/2000
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI
https://doi.org/10.2165/00003495-200060030-00007

Weitere Artikel der Ausgabe 3/2000

Drugs 3/2000 Zur Ausgabe

Adis Drug Evaluation

Meropenem

Adis Drug Evaluation

Metoprolol