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Pharmacology of the Meglitinide Analogs

New Treatment Options for Type 2 Diabetes Mellitus

  • Review Article
  • Published:
Treatments in Endocrinology

Abstract

The expression meglitinide analogs was introduced in 1995 to cover new molecules proposed as non-sulfonylurea insulinotropic agents and displaying structural analogy with meglitinide, such as repaglinide, nateglinide, and mitiglinide. Meglitinide analogs display, as judged by conformation analysis, a U-shaped configuration similar to that of antihyperglycemic sulfonylureas such as glibenclamide (glyburide) and glimepi-ride.

In rat pancreatic islets incubated in the presence of 7.0 mmol/L D-glucose, repaglinide and mitiglinide demonstrate comparable concentration-response relationships for stimulation of insulin release, with a threshold value <10 nmol/L and a maximal secretory response at about 10 nmol/L. Several findings indicate that meglitinide analogs provoke the closing of adenosine triphosphate-sensitive potassium channels, with subsequent gating of voltage-sensitive calcium channels. The effects of meglitinide analogs upon the binding of [3H]glibenclamide to islet cells membranes reinforces this concept. At variance, however, with other meglitinide analogs, the ionic and secretory response to repaglinide (10 μmol/L) is not rapidly reversible in perifused rat islets.

In experiments conducted in vivo in control and diabetic rats, repaglinide provokes a greater and more rapid increase in plasma insulin concentration and an earlier fall in glycemia than glibenclamide or glimepiride. Onset of effect is also more rapid and duration of effect shorter with nateglinide versus glibenclamide.

In clinical studies, single or repeated daily administration of repaglinide increased plasma insulin concentration in a dose-dependent manner, with an incremental peak reached about 2 hours after repaglinide intake. Plasma concentrations of repaglinide are about 5.0 μg/L 2–2.5 hours after oral intake of the drug. Despite the slow reversibility of repaglinide action in vitro, this drug offers advantages over glibenclamide in terms of the possible occurrence of hypoglycemia if a meal is missed.

In volunteers receiving a single oral dose of nateglinide (120mg) 10 minutes before a standardized 800 Kcal breakfast, the plasma insulin concentration was higher 5, 10, and 20 minutes after meal intake than when they received a single dose of repaglinide (0.5 or 2.0mg) or placebo 10 minutes before breakfast. Peak plasma concentrations of nateglinide were reached within 2 hours in most volunteers.

Peak plasma concentrations of mitiglinide were reached 30 minutes after a single oral dose in a representative volunteer. Mitiglinide significantly suppressed meal-induced elevations in blood glucose concentrations in a study of patients with type 2 diabetes.

In conclusion, two obvious differences among these meglitinide analogs should be underlined. First, on a molar basis, nateglinide is somewhat less potent than repaglinide or mitiglinide, as an insulinotropic agent. The maximal secretory responses evoked by these three meglitinide analogs are, however, identical to one another. Secondly, and as already mentioned, the functional effects of nateglinide and mitiglinide are more rapidly reversible than those of repaglinide, for instance in perifused rat islets. The meglitinide analogs offer the advantage over the long-acting antihyperglycemic sulfonylurea glibenclamide of minimizing the risk of undesirable hypoglycemia.

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References

  1. Malaisse WJ. Stimulation of insulin release by non-sulfonylurea hypoglycemic agents: the meglitinide family. Horm Metab Res 1995; 27: 263–6

    Article  PubMed  CAS  Google Scholar 

  2. Geisen K, Hitzel V, Ökomonopoulos R, et al. Inhibition of 3H-glibenclamide binding to sulfonylurea receptors by oral antidiabetics. Arzneimittel Forschung 1985; 35: 702–12

    Google Scholar 

  3. Lins L, Brasseur R, Malaise WJ. Conformational analysis of non-sulfonylurea hypoglycemic agents of the meglitinide family. Biochem Pharmacol 1995; 50: 1879–84

    Article  PubMed  CAS  Google Scholar 

  4. Garrino M-G, Meissner H-P, Henquin J-C. The non-sulfonylurea moiety of gliquidone mimics the effect of the parent molecule on pancreatic B-cells. Eur J Pharmacol 1986; 124: 309–16

    Article  PubMed  CAS  Google Scholar 

  5. Garcia-Martinez JA, Villanueva-Peñacarrillo ML, Valverde I, et al. Insulinotropic action of the non-sulfonylurea moiety of gliquidone in anaesthetized rats. Med sci Res 1997; 25: 807–9

    CAS  Google Scholar 

  6. Pratley RE, Foley JE, Dunning BE. Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiological approach to improve glucose control. Curr Pharm Des 2001; 7: 1375–97

    Article  PubMed  CAS  Google Scholar 

  7. Dunning BE. New non-sulfonylurea insulin secretagogues. Expert Opin Investig Drugs 1997; 6: 1041–8

    Article  PubMed  CAS  Google Scholar 

  8. Perfetti R, Mathur R, Egan JE. New insulin secretagogues for the treatment of type 2 diabetes. Dis Manag Clin Outcomes 1998; 1: 129–35

    Article  Google Scholar 

  9. Perfetti R, Barnett PS, Mathur R, et al. Novel therapeutic strategies for the treatment of type 2 diabetes. Diabetes Metab Rev 1998; 14: 207–25

    Article  PubMed  CAS  Google Scholar 

  10. Landgraf R. Meglitinide analogues in the treatment of type 2 diabetes mellitus. Drugs Aging 2000; 17: 411–25

    Article  PubMed  CAS  Google Scholar 

  11. Dornhorst A. Insulinotropic meglitinide analogues. Lancet 2001; 358: 1709–16

    Article  PubMed  CAS  Google Scholar 

  12. Malaisse WJ. Mechanism of action of a new class of insulin secretagogues. Exp Clin Endocrinol Diabetes 1999; 107Suppl. 4: S140–3

    Article  PubMed  CAS  Google Scholar 

  13. Culy CR, Jarvis B. Repaglinide: a review of its therapeutic use in type 2 diabetes mellitus. Drugs 2001; 61: 1625–60

    Article  PubMed  CAS  Google Scholar 

  14. Bakkali Nadi A, Malaisse-Lagae F, Malaisse WJ. Ionophoretic activity of meglitinide analogues. Diabetes Res 1994; 27: 61–71

    PubMed  CAS  Google Scholar 

  15. Lins L, Brasseur R, Malaisse WJ. Conformation analysis of the calcium complexes formed by meglitinide analogs. Res Commun Mol Pathol Pharmacol 1995; 90: 153–64

    PubMed  CAS  Google Scholar 

  16. Bakkali Nadi A, Malaisse-Lagae F, Malaisse WJ. Insulinotropic action of meglitinide analogs: concentrations-response relationship and nutrient dependency. Diabetes Res 1994; 27: 81–7

    Google Scholar 

  17. Louchami K, Jijakli H, Sener A, et al. Effect of repaglinide upon nutrient metabolism, biosynthetic activity, cationic fluxes and insulin release in rat pancreatic islets. Res Commun Mol Pathol Pharmacol 1998; 99: 155–68

    PubMed  CAS  Google Scholar 

  18. Van Onderbergen A, Malaisse-Lagae F, Malaisse WJ. Failure of meglitinide analogues to augment Ba2+-induced insulin release. Med sci Res 1995; 23: 371–2

    Google Scholar 

  19. 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: 111–4

    Article  PubMed  CAS  Google Scholar 

  20. Jijakli H, Ulusoy S, Malaisse WJ. Dissociation between the potency and reversibility of the insulinotropic action of two meglitinide analogues. Pharmacol Res 1996; 34: 105–8

    Article  PubMed  CAS  Google Scholar 

  21. Viñambres C, Villanueva-Peñacarrillo ML, Valverde I, et al. Repaglinide preserves nutrient-stimulated biosynthetic activity in rat pancreatic islets. Pharmacol Res 1996; 34: 83–5

    Article  PubMed  Google Scholar 

  22. Gromada J, Dissing S, Kofod H, et al. Effects of the hypoglycaemic drugs repaglinide and glibenclamide on ATP-sensitive potassium-channels and cytosolic calcium levels in βTC3 cells and rat pancreatic beta cells. Diabetologia 1995; 38: 1025–32

    Article  PubMed  CAS  Google Scholar 

  23. Fuhlendorff J, Rorsman P, Kofod H, et al. Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes. Diabetes 1998; 47: 345–51

    Article  PubMed  CAS  Google Scholar 

  24. Hu S, Wang S, Dunning BE. Tissue selectivity of antidiabetic agent nateglinide: study on cardiovascular and β-cell Katp channels. J Pharmacol Exp Ther 1999; 291: 1372–9

    PubMed  CAS  Google Scholar 

  25. Hu S, Wang S, Fanelli B, et al. Pancreatic β-cell Katp channel activity and membrane-binding studies with nateglinide: a comparison with sulfonylureas and repaglinide. J Pharmacol Exp Ther 2000; 293: 444–52

    PubMed  CAS  Google Scholar 

  26. Leclercq-Meyer V, Ladrière L, Fuhlendorff J, et al. Stimulation of insulin and somatostatin release by two meglitinide analogs. Endocrine 1997; 7: 311–7

    Article  PubMed  CAS  Google Scholar 

  27. Louchami K, Ladrière L, Jijakli H, et al. Effect of repaglinide upon insulin secretion in islets from rats infused for two days with a hypertonic solution of D-glucose. Endocrine 1998; 8: 247–50

    Article  PubMed  CAS  Google Scholar 

  28. Ladrière L, Malaisse-Lagae F, Fulhendorff J, et al. Repaglinide, glibenclamide and glimepiride administration to normal and hereditarily diabetic rats. Eur J Pharmacol 1997; 335: 227–34

    Article  PubMed  Google Scholar 

  29. Ladrière L, Malaisse-Lagae F, Malaisse WJ. Effect of antidiabetic agents on the increase in glycemia and insulinemia caused by refeeding in hereditarily diabetic rats. Res Commun Mol Pathol Pharmacol 1997; 97: 53–9

    PubMed  Google Scholar 

  30. Laghmich A, Ladrière L, Malaisse-Lagae F, et al. Pancreatic islet responsiveness to D-glucose after repeated administration of repaglinide. Eur J Pharmacol 1998; 348: 265–70

    Article  PubMed  CAS  Google Scholar 

  31. Ampudia-Blasco FJ, Heinemann L, Bender R, et al. Comparative dose-related time-action profiles of glibenclamide and a new non-sulphonylurea drug, AGEE 623 ZW, during euglycaemic clamp in healthy subjects. Diabetologia 1994; 37: 703–7

    Article  PubMed  CAS  Google Scholar 

  32. Juhl CB, Pørksen N, Hollingdal M, et al. Repaglinide acutely amplifies pulsatile insulin secretion by augmentation of burst mass with no effect on burst frequency. Diabetes Care 2000; 23: 675–81

    Article  PubMed  CAS  Google Scholar 

  33. Owens DR, Luzio SD, Ismail I, et al. Increased prandial insulin secretion after administration of a single preprandial oral dose of repaglinide in patients with type 2 diabetes. Diabetes Care 2000; 23: 518–23

    Article  PubMed  CAS  Google Scholar 

  34. Wolffenbuttel BH, Nijst L, Sels JPJE, et al. Effects of a new oral hypoglycaemic agent, repaglinide, on metabolic control in sulphonylurea-treated patients with NIDDM. Eur J Clin Pharmacol 1993; 45: 113–6

    Article  PubMed  CAS  Google Scholar 

  35. Strange P, Schwartz SL, Graf RJ, et al. Pharmacokinetics, pharmacodynamics and dose-response relationships of repaglinide in type 2 diabetes. Diabetes Technol Ther 1999; 1: 247–56

    Article  PubMed  CAS  Google Scholar 

  36. Damsbo P, Clauson P, Marbury TC, et al. A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients. Diabetes Care 1999; 22: 789–94

    Article  PubMed  CAS  Google Scholar 

  37. Damsbo P, Marbury TC, Hatorp V, et al. Flexible prandial glucose regulation with repaglinide in patients with type 2 diabetes. Diabetes Res Clin Pract 1999; 45: 31–9

    Article  PubMed  CAS  Google Scholar 

  38. Hatorp V, Bayer T. Repaglinide bioavailability in the fed or fasting state [abstract]. J Clin Pharmacol 1997; 37: 875

    Google Scholar 

  39. Hatorp V, Oliver S, Su C-APF. Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers. Int J Clin Pharmacol Ther 1998; 36: 636–41

    PubMed  CAS  Google Scholar 

  40. van Heiningen PNM, Hatorp V, Kramer Nielsen K, et al. Absorption, metabolism and excretion of a single oral dose of 14C-repaglinide during repaglinide multiple dosing. Eur J Clin Pharmacol 1999; 55: 521–5

    Article  PubMed  Google Scholar 

  41. Perentesis GP, Damsbo P, Müller PG, et al. Single dose pharmacokinetics and pharmacodynamics of repaglinide in type II diabetic patients [abstract]. J Clin Phamacol 1994; 34: 1021

    Google Scholar 

  42. Hedberg TG, Huang W-C. Repaglinide: a double-blind, randomized dose-response study [abstract]. Diabetologia 1998; 41Suppl. 1: A235

    Google Scholar 

  43. Hatorp V, Huang W-C, Strange P. Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes. J Clin Endocrinol Metab 1999; 84: 1475–8

    Article  PubMed  CAS  Google Scholar 

  44. Hatorp V, Walther KG, Christensen MS, et al. Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease. J Clin Pharmacol 2000; 40: 142–52

    Article  PubMed  CAS  Google Scholar 

  45. Marbury TC, Ruckle JL, Hatorp V, et al. Pharmacokinetics of repaglinide in subjects with renal impairment. Clin Pharmacol Ther 2000; 67: 7–15

    Article  PubMed  CAS  Google Scholar 

  46. Schumacher S, Abbasi I, Weise D, et al. Single and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment. Eur J Clin Pharmacol 2001; 57: 147–52

    Article  PubMed  CAS  Google Scholar 

  47. Horton ES, Clinkingbeard C, Gatlin M, et al. Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes. Diabetes Care 2000; 23: 1660–5

    Article  PubMed  CAS  Google Scholar 

  48. Bakkali Nadi A, Malaisse-Lagae F, Malaisse WJ. Ionophoretic properties of the non-sulphonylurea hypoglycaemic agents A-4166 and KAD-1229. Res Commun Mol Pathol Pharmacol 1995; 88: 339–47

    PubMed  CAS  Google Scholar 

  49. Malaisse-Lagae F, Malaisse WJ. Fate of 3H- and 14C-labelled A-4166 in pancreatic islets. Acta Diabetol 1996; 33: 298–300

    Article  PubMed  CAS  Google Scholar 

  50. Jijakli H, Ulusoy S, Malaisse WJ. Dynamics of the cationic and secretory responses to A-4166 in perifused pancreatic islets. Fundam Clin Pharmacol 1997; 11: 300–4

    Article  PubMed  CAS  Google Scholar 

  51. 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 1999; 134: 1395–400

    Article  Google Scholar 

  52. Malaisse WJ, Sener A. Effect of N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine on nutrient catabolism in rat pancreatic islets. Gen Pharmacol 1998; 31: 451–4

    Article  PubMed  CAS  Google Scholar 

  53. Viñambres C, Garcia-Martinez JA, Villanueva-Peñacarrillo ML, et al. Preservation of nutrient-stimulated biosynthetic activity in pancreatic islets exposed to a meglitinide analogue. Med sci Res 1995; 23: 779–80

    Google Scholar 

  54. Jijakli H, Malaisse WJ. Preservation of protein biosynthesis in rat pancreatic islets exposed to A-4166. Med sci Res 1997; 25: 813–4

    CAS  Google Scholar 

  55. Hu S, Wang S, Dunning BE. Effectiveness of nateglinide on in vitro insulin secretion from rat pancreatic islets desensitized to sulfonylureas. Int J Exp Diabetes Res 2001; 2: 73–9

    Article  PubMed  CAS  Google Scholar 

  56. Hu S, Wang S, Dunning BE. Glucose-dependent and glucose-sensitizing insulino-tropic effect of nateglinide: comparison to sulfonylureas and repaglinide. Int J Exp Diabetes Res 2001; 2: 63–72

    Article  PubMed  CAS  Google Scholar 

  57. Garcia-Martinez JA, Vifiambres C, Villanueva-Peñacarrillo ML, et al. Comparison and synergism between the insulinotropic action of succinic acid monomethyl ester and N-[(trans-4-isopropylcyclohexyl)-carbonyl]-D-phenylalanine. Med sci Res 1995; 23: 777–8

    CAS  Google Scholar 

  58. Laghmich A, Ladrière L, Dannacher H, et al. New esters of succinic acid and mixed molecules formed by such esters and a meglitinide analog: study of their insulinotropic potential. Pharmacol Res 2000; 41: 543–54

    Article  PubMed  CAS  Google Scholar 

  59. Ladrière L, Björkling F, Malaisse WJ. Stimulation of insulin release in hereditarily diabetic rats by mixed molecules formed of nateglinide and a succinic acid ester. Int J Mol Med 2000; 5: 63–5

    PubMed  Google Scholar 

  60. Laghmich A, Ladrière L, Malaisse-Lagae F, et al. Long-term effects of glibenclamide and nateglinide upon pancreatic islet function in normal and diabetic rats. Pharmacol Res 1999; 40: 475–82

    Article  PubMed  CAS  Google Scholar 

  61. Courtois P, Jijakli H, Ladrière B, et al. Pharmacodynamics, insulinotropic action and hypoglycemic effect of nateglinide and glibenclamide in normal and diabetic rats. Int J Mol Med 2003; 11: 105–9

    PubMed  CAS  Google Scholar 

  62. Kalbag JB, Water YH, Nedelman JR, et al. Mealtime glucose regulation with nateglinide in healthy volunteers: comparison with repaglinide and placebo. Diabetes Care 2001; 24: 73–7

    Article  PubMed  CAS  Google Scholar 

  63. Whitelaw DC, Clark PM, Smith JM, et al. Effects of the new oral hypoglycaemic agent nateglinide on insulin secretion in type 2 diabetes mellitus. Diabet Med 2000; 17: 225–9

    Article  PubMed  CAS  Google Scholar 

  64. 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; 23: 202–7

    Article  PubMed  CAS  Google Scholar 

  65. 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: 1081–6

    Article  PubMed  CAS  Google Scholar 

  66. Walter YH, Spratt DI, Garreffa S, et al. Mealtime glucose regulation by nateglinide in type-2 diabetes mellitus. Eur J Clin Pharmacol 2000; 56: 129–33

    Article  PubMed  CAS  Google Scholar 

  67. Hollander PA, Schwartz SL, Gatlin MR, et al. Nateglinide, but not glyburide, selectively enhances early insulin release and more efficiently controls postmeal glucose excursions with less total insulin exposure [abstract]. Diabetes 2000; 49Suppl. 1: A111

    Google Scholar 

  68. Hirschberg Y, Karara AH, Pietri AO, et al. Improved control of mealtime glucose excursions with coadministration of nateglinide and metformin. Diabetes Care 2000; 23: 349–53

    Article  PubMed  CAS  Google Scholar 

  69. Choudhury S, Hirschberg Y, Filipek R, et al. Single-dose pharmacokinetics of nateglinide in subjects with hepatic cirrhosis. J Clin Pharmacol 2000; 40: 634–40

    Article  PubMed  CAS  Google Scholar 

  70. Ohnota H, Koizumi T, Tsutsumi N, et al. Novel rapid- and short-acting hypoglycemic agent, a calcium(2s)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcar-bonyl) propionate (KAD-1229) that acts on the sulfonylurea receptor: comparison of effects between KAD-1229 and gliclazide. J Pharmacol Exp Ther 1994; 269: 489–95

    PubMed  CAS  Google Scholar 

  71. Mogami H, Shibata H, Nobusawa R, et al. Inhibition of ATP-sensitive K+ channel by a non-sulfonylurea compound KAD-1229 in a pancreatic β-cell line, MIN 6 cell. Eur J Pharmacol 1994; 269: 293–8

    Article  PubMed  CAS  Google Scholar 

  72. Lins L, Brasseur R, Malaisse WJ, et al. Importance of the hydrophobic energy: structural determinant of a hypoglycemic drug of the meglitinide family by nuclear magnetic resonance and molecular modelling. Biochem Pharmacol 1996; 52: 1155–68

    Article  PubMed  CAS  Google Scholar 

  73. Malaisse WJ, Sato F. Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl) propionate: I. Secretory and cationic aspects. Gen Pharmacol 1995; 26: 1313–8

    Article  PubMed  CAS  Google Scholar 

  74. Malaisse WJ, Dard-Brunelle B. Binding of tritiated S21403 to an artificial phospholipid bilayer. Res Commun Mol Pathol Phamacol 1999; 103: 268–74

    Google Scholar 

  75. Malaisse WJ, Bakkali Nadi A, Malaisse-Lagae F, et al. Insulinotropic action of (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarbonyl)propionate: II. Ionophoretic and conformational aspects. Gen Pharmacol 1995; 26: 1319–25

    Article  PubMed  CAS  Google Scholar 

  76. Ohnota H, Kobayahi M, Koizumi T, et al. In vitro insulinotropic action of a new non-sulfonylurea hypoglycemic agent, calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinyl-carbonyl) propionate dihydrate (KAD-1229), in rat pancreatic B-cells. Biochem Pharmacol1995; 49: 165–71

    Article  PubMed  CAS  Google Scholar 

  77. Van Onderbergen A, Malaisse-Lagae F, Malaisse WJ. Effects of ATP and hypoglycemic agents on 45Ca uptake by subcellular fractions prepared from rat pancreatic islets. Med sci Res 1995; 23: 843–4

    Google Scholar 

  78. Ulusoy S, Malaisse WJ. Effect of the meglitinide analogue KAD-1229 on 45Ca outflow and insulin release in pancreatic islets. Diab Res 1996; 31: 27–31

    CAS  Google Scholar 

  79. Louchami K, Jijakli H, Malaisse WJ. Effect of the meglitinide analog S21403 on cationic fluxes and insulin release in perifused rat pancreatic islets exposed to a high concentration of D-glucose. Pharmacol Res 1999; 40: 297–300

    Article  PubMed  CAS  Google Scholar 

  80. Reimann F, Proks P, Ashcroft FM. Effects of mitiglinide (S21403) on Kir6.2/ SUR2A and Kir6.2/SUR2B types of ATP-sensitive potassium channel. Br J Pharmacol 2001; 132: 1542–8

    Article  PubMed  CAS  Google Scholar 

  81. Ohnota H, Koizumi T, Kobayashi M, et al. Normalization of impaired glucose tolerance by the short-acting hypoglycemic agent calcium (2S)-2-benzyl-3-(cis-hexahydro-2-isoindolinylcarboxyl) propionate dihydrate (KAD-1229) in non-insulin-dependent diabetes mellitus rats. Can J Physiol Pharmacol 1995; 73: 1–6

    Article  PubMed  CAS  Google Scholar 

  82. Martin D, Bouzom F, Merdjan H. Building of a physiologically based mathematical model for dynamics of an antidiabetic agent. In: Third International Symposium on Measurements and Kinetics of In Vivo Drug Effects. Advances in simultaneous pharmacokinetic/pharmacodynamic modelling; 1988 May 27–30; Noordwijkerhout, The Netherlands. Leiden/Amsterdam: Center for Drug Research, 1998: 168–70

    Google Scholar 

  83. Yamada N, Shigeta Y, Kaneko T, et al. Hypoglycemic effects and safety of a novel rapid-acting insulinotropic agent, KAD-1229, for NIDDM [abstract]. Diabetes 1996; 45Suppl. 2: 74A

    Google Scholar 

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Malaisse, W.J. Pharmacology of the Meglitinide Analogs. Mol Diag Ther 2, 401–414 (2003). https://doi.org/10.2165/00024677-200302060-00004

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