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Insulin analogues: New therapies for type 2 diabetes mellitus

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Abstract

Insulin therapy is ultimately necessary for the control of blood glucose in a majority of patients with type 2 diabetes mellitus. Unfortunately, the pharmacokinetic characteristics of previously available rapid-, intermediate-, and long-acting preparations make sustained normoglycemia almost impossible. Advances in molecular genetic engineering have made possible the development of insulin analogues with pharmacokinetics that more closely mimic the needs of patients with type 2 diabetes. In the following article, we explore the insulin analogues currently available for clinical use, their pharmacokinetics, and the rationale for their use in the treatment of type 2 diabetes, and follow-up with a brief examination of future developments.

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References and Recommended Reading

  1. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study Group [no authors listed]. Lancet 1998, 352:837–853.This is a large-scale multicenter trial demonstrating the importance of glucose control in patients with type 2 diabetes. Adequate glucose control often requires the use of insulin.

  2. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group [no authors listed]. N Engl J Med 1993, 329:977–986.

  3. Fertig BJ, Simmons DA, Martin DB: Therapy for diabetes. In Diabetes in America. Edited by Harris MI et al. Bethesda, MA: NIH; 1995:Publication No. 95-1469.

    Google Scholar 

  4. Perley MJ, Kipnis DM: Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967, 46:1954–1962.

    PubMed  CAS  Google Scholar 

  5. Srikanta S, Ganda OP, Gleason RE, et al.: Pre-type 1 diabetes: linear loss of beta-cell response to intravenous glucose. Diabetes 1984, 33:717–720.

    Article  PubMed  CAS  Google Scholar 

  6. Ward WK, Bolgiano DC, McKnight B, et al.: Diminshed B-cell secretory capacity in patients with noninsulin dependent diabetes mellitus. J Clin Invest 1984, 76:1318–1328.

    Article  Google Scholar 

  7. Bagdade JD, Bierman EL, Porte D Jr: The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest 1967, 46:1549–1557.

    PubMed  CAS  Google Scholar 

  8. Vajo Z, Fawcett J, Duckworth WC: Recombinant DNA technology in the treatment of diabetes: insulin analogs. Endocr Rev 2001, 22:706–717.

    Article  PubMed  CAS  Google Scholar 

  9. Bolli GB, Di Marchi RD, Park GD, et al.: Insulin analogues and their potential in the management of diabetes mellitus. Diabetologia 1999, 42:1151–1167.

    Article  PubMed  CAS  Google Scholar 

  10. Bruttomesso D, Pianta A, Mari A, et al.: Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients. Diabetes 1999, 48:99–105.

    Article  PubMed  CAS  Google Scholar 

  11. Feinglos MN, Thacker CH, English J: Modification of postprandial hyperglycemia with insulin lispro improves glucose control in patients with type 2 diabetes. Diabetes Care 1997, 20:1539–1542.

    Article  PubMed  CAS  Google Scholar 

  12. Bastyr EJ3rd, Stuart CA, Brodows RG, et al.: Therapy focused on lowering post-prandial glucose, not fasting glucose, may be superior for lowering HbA1c. Diabetes Care 2000, 23:1236–1241. Demonstrates the importance of short-acting insulin analogues in the treatment of type 2 diabetes.

    Article  PubMed  CAS  Google Scholar 

  13. Anderson JH, Brunelle RL, Keohane P, et al.: Mealtime treatment with insulin analog improves post-prandial hyperglycemia and hypoglycemia in patients with noninsulin-dependent diabetes mellitus. Arch Intern Med 1997, 157:1249–1255.

    Article  PubMed  CAS  Google Scholar 

  14. Strachan MW, Frier BM: Optimal time of administration of insulin lispro. Diabetes Care 1998, 21:26–31.

    Article  PubMed  CAS  Google Scholar 

  15. Setter SM, Corbett CF, Campbell RK, White JR: Insulin aspart: a new rapid-acting insulin analog. Ann Pharmacotherapy 2000, 34:1423–1431.

    CAS  Google Scholar 

  16. Hedman CA, Lindstrom T, Arnqvist HJ: Direct comparison of insulin lispro and aspart shows small differences in plasma insulin profiles after subcutaneous injection in type 1 diabetes. Diabetes Care 2001, 24:1120–1121.

    Article  PubMed  CAS  Google Scholar 

  17. Rosenfalck AM, Thorsby P, Kjems L, et al.: Improved post-prandial glycaemic control with insulin Aspart in type 2 diabetic patients treated with insulin. Acta Diabetol 2000, 37:41–46.

    Article  PubMed  CAS  Google Scholar 

  18. Raskin P, et al.: Human insulin analog (insulin aspart, Iasp) is comparable to human insulin (HI) in type 2 diabetes (abstract 1554). Diabetes 1999, 48(suppl 1):A355.

    Google Scholar 

  19. Home PD, Lindholm A, Hylleberg B, Round P: Improved glycemic control with insulin aspart: a multicentre randomized, double blind cross-over trial in type 1 diabetic patients. Diabetes Care 1998, 21:1904–1909.

    Article  PubMed  CAS  Google Scholar 

  20. Home PD, Lindholm A, Riis A, et al.: Insulin aspart vs human insulin in the management of long-term blood glucose control in type 1 diabetes mellitus: a randomized controlled trial. European Insulin Aspart Study Group. Diabet Med 2000, 17:762–770.

    Article  PubMed  CAS  Google Scholar 

  21. Bolli GB, Owens DR: Insulin glargine. Lancet 2000, 356:443–444.

    Article  PubMed  CAS  Google Scholar 

  22. Yki-Jarvinen H, Dressler A, Ziemen M: Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care 2000, 23:1130–1136. Illustrates the importance of a long-acting insulin analogue in the treatment of type 2 diabetes mellitus.

    Article  PubMed  CAS  Google Scholar 

  23. Rosenstock J, Schwartz SL, Clark CMJr, et al.: Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001, 24:631–636.

    Article  PubMed  CAS  Google Scholar 

  24. Brunner GA, Sendhofer G, Wutte A, et al.: Pharmacokinetic and pharmacodynamic properties of long-acting insulin analogue NN304 in comparison to NPH insulin in humans. Exp Clin Endocrinol Diabetes 2000, 108:100–105.

    Article  PubMed  CAS  Google Scholar 

  25. Markussen J, Havelund S, Kurtzhals P, et al.: Soluble, fatty acid acylated insulins bind to albumin and show protracted action in pigs. Diabetologia 1996, 39:281–288.

    PubMed  CAS  Google Scholar 

  26. Kurtzhals P, Havelund S, Jonassen I, Markussen J: Effect of fatty acids and selected drugs on the albumin binding of a long-acting, acylated isnulin analogue. J Pharmac Sci 1997, 86:1365–1368.

    Article  CAS  Google Scholar 

  27. Reaven GM: Insulin resistance and compensatory hyperinsulinemia: role in hypertension, dyslipidemia, and coronary heart disease. Am Heart J 1991, 4:1283–1288.

    Article  Google Scholar 

  28. Sönksen PH, Russell-Jones D, Jones RH: Growth hormone and diabetes mellitus. A review of sixty-three years of medical research and a glimpse into the future. Horm Res 1993, 40:68–79.

    Article  PubMed  Google Scholar 

  29. Shojaee-Moradie F, Powrie JK, Sundermann E, et al.: Novel hepatoselective insulin analog: studies with a covalently linked thyroxyl-insulin complex in humans. Diabetes Care 2000, 23:1124–1129.

    Article  PubMed  CAS  Google Scholar 

  30. Cefalu WT, Skyler JS, Kourides IA, et al.: Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med 2001, 134:203–207.

    PubMed  CAS  Google Scholar 

  31. Clement S, Still JG, Kosutic G, et al.: A dose-escalation study of the effects of two sequential doses of oral modified insulin on blood glucose concentrations in patients with type 1 diabetes mellitus. Diabetes 2001, 50(suppl 2):A109.

    Google Scholar 

  32. Dandona P, Clement S, Still JG, et al.: Effect of an oral modified insulin on blood glucose levels in fasting and fed type 1 diabetic patients receiving a "basal" regimen of injected insulin. Diabetes 2001, 50(suppl 2):A44.

    Google Scholar 

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Authors and Affiliations

  1. Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Box 3921, 27710, Durham, NC, USA

    Mark N. Feinglos MD, CM

Authors
  1. M. Angelyn Bethel MD
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  2. Mark N. Feinglos MD, CM
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Bethel, M.A., Feinglos, M.N. Insulin analogues: New therapies for type 2 diabetes mellitus. Curr Diab Rep 2, 403–408 (2002). https://doi.org/10.1007/s11892-002-0104-4

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  • DOI: https://doi.org/10.1007/s11892-002-0104-4

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