Skip to main content
NCBI home page
Journal of the National Medical Association logoLink to Journal of the National Medical Association
. 2007 Apr;99(4):357-60, 363-7.

New therapeutic options for treating type-2 diabetes: a review of insulin analogs and premixed insulin analogs.

Charles Choe 1, Steve Edelman 1
PMCID: PMC2569656  PMID: 17444424

Abstract

There is a growing consensus that blood glucose control, and postprandial control in particular, must become more aggressive if we are to stem the growing tide of diabetes-related complications and mortality. For most patients, this means that insulin therapy must begin earlier and that insulin must be titrated sufficiently to achieve tighter glycemic targets. The limitations of traditional treatment regimens, delivery devices and conventional insulin formulations, in conjunction with patient factors, have prevented the majority of people with type-2 diabetes from realizing the potential benefits of insulin therapy and achieving recommended glycemic targets. Fortunately, modern insulin analog formulations, new treatment regimens, and advanced delivery devices are now available. This review will discuss features of these new tools, and compare the benefits of using premixed insulin versus a basal-only approach to initiating insulin therapy. Once physicians become familiar with these tools and incorporate them into daily practice, they will be able to better tailor diabetes self-management programs to the needs of individual patients. The result will be that more patients should be able to reach recommended glycemic targets with greater convenience and safety than has previously been available.

Full text

PDF
357

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abstracts of the 66th Scientific Sessions of the American Diabetes Association, June 9-13, 2006, Washington, DC, USA. Diabetes. 2006 Jun;55(Suppl 1):A1–617. [PubMed] [Google Scholar]
  2. Abstracts of the 66th Scientific Sessions of the American Diabetes Association, June 9-13, 2006, Washington, DC, USA. Diabetes. 2006 Jun;55(Suppl 1):A1–617. [PubMed] [Google Scholar]
  3. Alberti George, Zimmet Paul, Shaw Jonathan, Bloomgarden Zachary, Kaufman Francine, Silink Martin, Consensus Workshop Group Type 2 diabetes in the young: the evolving epidemic: the international diabetes federation consensus workshop. Diabetes Care. 2004 Jul;27(7):1798–1811. doi: 10.2337/diacare.27.7.1798. [DOI] [PubMed] [Google Scholar]
  4. Becker R. H. A., Frick A. D., Burger F., Scholtz H., Potgieter J. H. A comparison of the steady-state pharmacokinetics and pharmacodynamics of a novel rapid-acting insulin analog, insulin glulisine, and regular human insulin in healthy volunteers using the euglycemic clamp technique. Exp Clin Endocrinol Diabetes. 2005 May;113(5):292–297. doi: 10.1055/s-2005-865637. [DOI] [PubMed] [Google Scholar]
  5. Bell David S. H. The case for combination therapy as first-line treatment for the type 2 diabetic patient. Treat Endocrinol. 2006;5(3):131–137. doi: 10.2165/00024677-200605030-00001. [DOI] [PubMed] [Google Scholar]
  6. Bergenstal Richard M. Treatment models from the International Diabetes Center: advancing from oral agents to insulin therapy in type 2 diabetes. Endocr Pract. 2006 Jan-Feb;12 (Suppl 1):98–104. doi: 10.4158/EP.12.S1.98. [DOI] [PubMed] [Google Scholar]
  7. Bohannon N. J. Insulin delivery using pen devices. Simple-to-use tools may help young and old alike. Postgrad Med. 1999 Oct 15;106(5):57-8, 61-4, 68. doi: 10.3810/pgm.1999.10.15.751. [DOI] [PubMed] [Google Scholar]
  8. Brown Jonathan B., Nichols Gregory A., Perry Andrew. The burden of treatment failure in type 2 diabetes. Diabetes Care. 2004 Jul;27(7):1535–1540. doi: 10.2337/diacare.27.7.1535. [DOI] [PubMed] [Google Scholar]
  9. Cappelleri Joseph C., Cefalu William T., Rosenstock Julio, Kourides Ione A., Gerber Robert A. Treatment satisfaction in type 2 diabetes: a comparison between an inhaled insulin regimen and a subcutaneous insulin regimen. Clin Ther. 2002 Apr;24(4):552–564. doi: 10.1016/s0149-2918(02)85131-1. [DOI] [PubMed] [Google Scholar]
  10. Cefalu W. T., Skyler J. S., Kourides I. A., Landschulz W. H., Balagtas C. C., Cheng S., Gelfand R. A., Inhaled Insulin Study Group Inhaled human insulin treatment in patients with type 2 diabetes mellitus. Ann Intern Med. 2001 Feb 6;134(3):203–207. doi: 10.7326/0003-4819-134-3-200102060-00011. [DOI] [PubMed] [Google Scholar]
  11. Chan Jean L., Abrahamson Martin J. Pharmacological management of type 2 diabetes mellitus: rationale for rational use of insulin. Mayo Clin Proc. 2003 Apr;78(4):459–467. doi: 10.4065/78.4.459. [DOI] [PubMed] [Google Scholar]
  12. Cowie Catherine C., Rust Keith F., Byrd-Holt Danita D., Eberhardt Mark S., Flegal Katherine M., Engelgau Michael M., Saydah Sharon H., Williams Desmond E., Geiss Linda S., Gregg Edward W. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health And Nutrition Examination Survey 1999-2002. Diabetes Care. 2006 Jun;29(6):1263–1268. doi: 10.2337/dc06-0062. [DOI] [PubMed] [Google Scholar]
  13. Cramer Joyce A. A systematic review of adherence with medications for diabetes. Diabetes Care. 2004 May;27(5):1218–1224. doi: 10.2337/diacare.27.5.1218. [DOI] [PubMed] [Google Scholar]
  14. DECODE Study Group, the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001 Feb 12;161(3):397–405. doi: 10.1001/archinte.161.3.397. [DOI] [PubMed] [Google Scholar]
  15. DeFronzo Ralph A., Bergenstal Richard M., Cefalu William T., Pullman John, Lerman Sam, Bode Bruce W., Phillips Lawrence S., Exubera Phase III Study Group Efficacy of inhaled insulin in patients with type 2 diabetes not controlled with diet and exercise: a 12-week, randomized, comparative trial. Diabetes Care. 2005 Aug;28(8):1922–1928. doi: 10.2337/diacare.28.8.1922. [DOI] [PubMed] [Google Scholar]
  16. Del Prato S. Loss of early insulin secretion leads to postprandial hyperglycaemia. Diabetologia. 2002 Nov 12;46 (Suppl 1):M2–M8. doi: 10.1007/s00125-002-0930-6. [DOI] [PubMed] [Google Scholar]
  17. Dungan Kathleen M., Buse John B., Largay Joseph, Kelly Mary M., Button Eric A., Kato Shuhei, Wittlin Steven. 1,5-anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes. Diabetes Care. 2006 Jun;29(6):1214–1219. doi: 10.2337/dc06-1910. [DOI] [PubMed] [Google Scholar]
  18. Garber A. J., Wahlen J., Wahl T., Bressler P., Braceras R., Allen E., Jain R. Attainment of glycaemic goals in type 2 diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab. 2006 Jan;8(1):58–66. doi: 10.1111/j.1463-1326.2005.00563.x. [DOI] [PubMed] [Google Scholar]
  19. Gavin James R., 3rd How can we implement current therapies and interventions to achieve glycemic control? Endocr Pract. 2006 Jan-Feb;12 (Suppl 1):93–97. doi: 10.4158/EP.12.S1.93. [DOI] [PubMed] [Google Scholar]
  20. Haak T., Tiengo A., Draeger E., Suntum M., Waldhäusl W. Lower within-subject variability of fasting blood glucose and reduced weight gain with insulin detemir compared to NPH insulin in patients with type 2 diabetes. Diabetes Obes Metab. 2005 Jan;7(1):56–64. doi: 10.1111/j.1463-1326.2004.00373.x. [DOI] [PubMed] [Google Scholar]
  21. Harris M. I., Eastman R. C., Cowie C. C., Flegal K. M., Eberhardt M. S. Racial and ethnic differences in glycemic control of adults with type 2 diabetes. Diabetes Care. 1999 Mar;22(3):403–408. doi: 10.2337/diacare.22.3.403. [DOI] [PubMed] [Google Scholar]
  22. Heise Tim, Nosek Leszek, Rønn Birgitte Biilmann, Endahl Lars, Heinemann Lutz, Kapitza Christoph, Draeger Eberhard. Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes. Diabetes. 2004 Jun;53(6):1614–1620. doi: 10.2337/diabetes.53.6.1614. [DOI] [PubMed] [Google Scholar]
  23. Hermansen Kjeld, Davies Melanie, Derezinski Taudeusz, Martinez Ravn Gabrielle, Clauson Per, Home Philip. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006 Jun;29(6):1269–1274. doi: 10.2337/dc05-1365. [DOI] [PubMed] [Google Scholar]
  24. Homko Carol, Deluzio Antonio, Jimenez Carolyn, Kolaczynski Jerzy W., Boden Guenther. Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects. Diabetes Care. 2003 Jul;26(7):2027–2031. doi: 10.2337/diacare.26.7.2027. [DOI] [PubMed] [Google Scholar]
  25. Jeavons D., Hungin A. P. S., Cornford C. S. Patients with poorly controlled diabetes in primary care: healthcare clinicians' beliefs and attitudes. Postgrad Med J. 2006 May;82(967):347–350. doi: 10.1136/pgmj.2005.039545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Khaw K. T., Wareham N., Luben R., Bingham S., Oakes S., Welch A., Day N. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001 Jan 6;322(7277):15–18. doi: 10.1136/bmj.322.7277.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Khaw Kay-Tee, Wareham Nicholas, Bingham Sheila, Luben Robert, Welch Ailsa, Day Nicholas. Association of hemoglobin A1c with cardiovascular disease and mortality in adults: the European prospective investigation into cancer in Norfolk. Ann Intern Med. 2004 Sep 21;141(6):413–420. doi: 10.7326/0003-4819-141-6-200409210-00006. [DOI] [PubMed] [Google Scholar]
  28. Korytkowski Mary, Niskanen Leo, Asakura Toshinari. FlexPen: addressing issues of confidence and convenience in insulin delivery. Clin Ther. 2005;27 (Suppl B):S89–100. doi: 10.1016/j.clinthera.2005.11.019. [DOI] [PubMed] [Google Scholar]
  29. Lebovitz Harold E., Austin Mary M., Blonde Lawrence, Davidson Jaime A., Del Prato Stefano, Gavin James R., 3rd, Handelsman Yehuda, Jellinger Paul S., Levy Philip, Riddle Matthew C. ACE/AACE consensus conference on the implementation of outpatient management of diabetes mellitus: consensus conference recommendations. Endocr Pract. 2006 Jan-Feb;12 (Suppl 1):6–12. doi: 10.4158/EP.12.S1.6. [DOI] [PubMed] [Google Scholar]
  30. Leiter Lawrence A., Ceriello Antonio, Davidson Jaime A., Hanefeld Markolf, Monnier Louis, Owens David R., Tajima Naoko, Tuomilehto Jaakko, International Prandial Glucose Regulation Study Group Postprandial glucose regulation: new data and new implications. Clin Ther. 2005;27 (Suppl B):S42–S56. doi: 10.1016/j.clinthera.2005.11.020. [DOI] [PubMed] [Google Scholar]
  31. Lepore M., Pampanelli S., Fanelli C., Porcellati F., Bartocci L., Di Vincenzo A., Cordoni C., Costa E., Brunetti P., Bolli G. B. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000 Dec;49(12):2142–2148. doi: 10.2337/diabetes.49.12.2142. [DOI] [PubMed] [Google Scholar]
  32. Malone J. K., Bai S., Campaigne B. N., Reviriego J., Augendre-Ferrante B. Twice-daily pre-mixed insulin rather than basal insulin therapy alone results in better overall glycaemic control in patients with Type 2 diabetes. Diabet Med. 2005 Apr;22(4):374–381. doi: 10.1111/j.1464-5491.2005.01511.x. [DOI] [PubMed] [Google Scholar]
  33. Malone James K., Kerr Lisa F., Campaigne Barbara N., Sachson Richard A., Holcombe John H., Lispro Mixture-Glargine Study Group Combined therapy with insulin lispro Mix 75/25 plus metformin or insulin glargine plus metformin: a 16-week, randomized, open-label, crossover study in patients with type 2 diabetes beginning insulin therapy. Clin Ther. 2004 Dec;26(12):2034–2044. doi: 10.1016/j.clinthera.2004.12.015. [DOI] [PubMed] [Google Scholar]
  34. Monnier L., Benichou M., Charra-Ebrard S., Boegner C., Colette C. An overview of the rationale for pharmacological strategies in type 2 diabetes: from the evidence to new perspectives. Diabetes Metab. 2005 Apr;31(2):101–109. doi: 10.1016/s1262-3636(07)70174-x. [DOI] [PubMed] [Google Scholar]
  35. Monnier Louis, Lapinski Hélène, Colette Claude. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003 Mar;26(3):881–885. doi: 10.2337/diacare.26.3.881. [DOI] [PubMed] [Google Scholar]
  36. Mooradian Arshag D. Towards single-tablet therapy for type 2 diabetes mellitus. Rationale and recent developments. Treat Endocrinol. 2004;3(5):279–287. doi: 10.2165/00024677-200403050-00002. [DOI] [PubMed] [Google Scholar]
  37. Polonsky William H., Fisher Lawrence, Guzman Susan, Villa-Caballero Leonel, Edelman Steven V. Psychological insulin resistance in patients with type 2 diabetes: the scope of the problem. Diabetes Care. 2005 Oct;28(10):2543–2545. doi: 10.2337/diacare.28.10.2543. [DOI] [PubMed] [Google Scholar]
  38. Raskin Philip, Allen Elsie, Hollander Priscilla, Lewin Andrew, Gabbay Robert A., Hu Peter, Bode Bruce, Garber Alan, INITIATE Study Group Initiating insulin therapy in type 2 Diabetes: a comparison of biphasic and basal insulin analogs. Diabetes Care. 2005 Feb;28(2):260–265. doi: 10.2337/diacare.28.2.260. [DOI] [PubMed] [Google Scholar]
  39. Raslová K., Bogoev M., Raz I., Leth G., Gall M-A, Hâncu N. Insulin detemir and insulin aspart: a promising basal-bolus regimen for type 2 diabetes. Diabetes Res Clin Pract. 2004 Nov;66(2):193–201. doi: 10.1016/j.diabres.2004.03.003. [DOI] [PubMed] [Google Scholar]
  40. Resnick Helaine E., Foster Gregory L., Bardsley Joan, Ratner Robert E. Achievement of American Diabetes Association clinical practice recommendations among U.S. adults with diabetes, 1999-2002: the National Health and Nutrition Examination Survey. Diabetes Care. 2006 Mar;29(3):531–537. doi: 10.2337/diacare.29.03.06.dc05-1254. [DOI] [PubMed] [Google Scholar]
  41. Riddle Matthew C. Glycemic management of type 2 diabetes: an emerging strategy with oral agents, insulins, and combinations. Endocrinol Metab Clin North Am. 2005 Mar;34(1):77–98. doi: 10.1016/j.ecl.2004.12.002. [DOI] [PubMed] [Google Scholar]
  42. Riddle Matthew C., Rosenstock Julio, Gerich John, Insulin Glargine 4002 Study Investigators The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care. 2003 Nov;26(11):3080–3086. doi: 10.2337/diacare.26.11.3080. [DOI] [PubMed] [Google Scholar]
  43. Rosenstock J., Schwartz S. L., Clark C. M., Jr, Park G. D., Donley D. W., Edwards M. B. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care. 2001 Apr;24(4):631–636. doi: 10.2337/diacare.24.4.631. [DOI] [PubMed] [Google Scholar]
  44. Rosenstock Julio, Cappelleri Joseph C., Bolinder Björn, Gerber Robert A. Patient satisfaction and glycemic control after 1 year with inhaled insulin (Exubera) in patients with type 1 or type 2 diabetes. Diabetes Care. 2004 Jun;27(6):1318–1323. doi: 10.2337/diacare.27.6.1318. [DOI] [PubMed] [Google Scholar]
  45. Rosenstock Julio, Zinman Bernard, Murphy Liam J., Clement Stephen C., Moore Paul, Bowering C. Keith, Hendler Rosa, Lan Shu-Ping, Cefalu William T. Inhaled insulin improves glycemic control when substituted for or added to oral combination therapy in type 2 diabetes: a randomized, controlled trial. Ann Intern Med. 2005 Oct 18;143(8):549–558. doi: 10.7326/0003-4819-143-8-200510180-00005. [DOI] [PubMed] [Google Scholar]
  46. Weiss Stuart R., Cheng Shu-Lin, Kourides Ione A., Gelfand Robert A., Landschulz William H., Inhaled Insulin Phase II Study Group Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial. Arch Intern Med. 2003 Oct 27;163(19):2277–2282. doi: 10.1001/archinte.163.19.2277. [DOI] [PubMed] [Google Scholar]
  47. Wild Sarah, Roglic Gojka, Green Anders, Sicree Richard, King Hilary. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004 May;27(5):1047–1053. doi: 10.2337/diacare.27.5.1047. [DOI] [PubMed] [Google Scholar]
  48. Yki-Järvinen H. Combination therapies with insulin in type 2 diabetes. Diabetes Care. 2001 Apr;24(4):758–767. doi: 10.2337/diacare.24.4.758. [DOI] [PubMed] [Google Scholar]
  49. Yki-Järvinen H., Dressler A., Ziemen M., HOE 901/300s Study Group 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. HOE 901/3002 Study Group. Diabetes Care. 2000 Aug;23(8):1130–1136. doi: 10.2337/diacare.23.8.1130. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the National Medical Association are provided here courtesy of National Medical Association

RESOURCES