Уважаемые пользователи!

Данный сайт содержит информацию для людей с медицинским образованием и специалистов здравоохранения.
Входя на сайт, Вы подтверждаете свое согласие с Условиями использования и Политикой конфиденциальности.



Dear visitor!
This site contains medical information for healthcare professionals.
You can go further, if you agree with Terms and Conditions and Privacy Policy on this site.

Insulin degludec/insulin aspart is the first co-formulation of basal and prandial insulin analogues

Cover Page

Abstract


Achievement of glycemic control is the major therapeutic aim to prevent or delay the onset and progression of diabetes related complications. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. The aim for insulin therapy is to mimic the physiological profile of insulin secretion seen in nondiabetic patients. Development of the insulin analogs has offered new opportunities in the diabetes management to achieve greater safety and tolerability of diabetes treatment. Insulin degludec/insulin aspart(IDegAsp) (Ryzodeg?, Novo Nordisk, Denmark) is the first soluble co-formulation of 70% ultra-long acting insulin degludec and 30% rapid-acting prandial insulin aspart, providing both basal insulin coverage and a prandial insulin bolus in a single injection. This review discusses data regarding the efficacy, safety, tolerability and clinical benefits of IDegAsp. According to the clinical development program IDegAspprovides an achievement of similar glycemic control with superiority in lowering FPG with using less number of injections and lower daily insulin dose, and also associated with numerically lower rates of confirmed and nocturnal confirmed hypoglycaemia in comparison with premixed or basal insulin analogues, as well as a basal component for basal?bolus therapy with supplementary mealtime insulin aspart.Trial results suggest that IDegAspQD or BID maybe an appropriate and reasonable option for initiating insulin therapy in type 1 and type 2 diabetic patients inadequately controlled on maximal doses of oral antidiabetic drugs,and also a simple alternative to basal?bolus treatment in patients who require intensification of insulin therapy, especially when adherence to more complex regimens is challenging.

Ivan Ivanovich Dedov

Endocrinology Research Centre, Moscow

Email: dedov@endocrincentr.ru

Russian Federation MD, PhD, professor, academician of Russian Academy of Sciences, Director of Endocrinology Research Centre

Marina Vladimirovna Shestakova

Endocrinology Research Centre, Moscow; I.M.Sechenov First Moscow State Medical University, Moscow

Author for correspondence.
Email: nephro@endocrincentr.ru
https://www.researchgate.net/profile/Marina_Shestakova2

Russian Federation MD, PhD, professor, academician-fellow of Russian Academy of Sciences, Director of Diabetes Institute in Endocrinology Research Centre, head of the Pediatric endocrinology and diabetology Chair in I.M.Sechenov First Moscow State Medical University

  1. The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986.
  2. Stratton IM. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321(7258):405-412. Available from: http://www.bmj.com/cgi/doi/10.1136/bmj.321.7258.405 PubMed PMID: 10938048. doi: 10.1136/bmj.321.7258.405.
  3. Hoerger TJ, Segel JE, Gregg EW, Saaddine JB. Is Glycemic Control Improving in U.S. Adults. Diabetes Care 2007;31(1):81-86. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc07-1572 PubMed PMID: 17934153. doi: 10.2337/dc07-1572.
  4. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD(. Diabetologia 2012;55(6):1577-1596. Available from: http://link.springer.com/10.1007/s00125-012-2534-0 doi: 10.1007/s00125-012-2534-0.
  5. International Diabetes Federation . Global Guideline for Type 2 Diabetes. Clinical Guidelines Task Force. 2012.
  6. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. American Association of Clinical Endocrinologists' Comprehensive Diabetes Management Algorithm 2013 Consensus Statement. Endocrine Practice 2013;19(s2):327-336. Available from: http://aace.metapress.com/openurl.asp?genre=article&id=doi: 10.4158/EP13176.CSUPPL. PubMed PMID: 23598536. doi: 10.4158/EP13176.CSUPPL.
  7. Dedov II, Shestakova MV, Ametov AS, Antsiferov MB, Galstyan GR, Mayorov AY, et al. Russian Association of Endocrinologists expert consensus document on initiation and intensification of antyhyperglycaemic therapyin type 2 diabetes mellitus. Diabetes mellitus. 2011;(4):6-17. doi: 10.14341/2072-0351-5810.
  8. Dedov II, Shestakova MV, Aleksandrov AA, Galstyan GR, Grigoryan OR, Esayan RM, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV (6th edition. Diabetes mellitus 2013; (1S):1-120. Available from: http://endojournals.ru/index.php/dia/article/view/6274 doi: 10.14341/DM20131S1-121.
  9. Ryan EA, Imes S, Wallace C. Short-Term Intensive Insulin Therapy in Newly Diagnosed Type 2 Diabetes. Diabetes Care 2004;27(5):1028-1032. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.27.5.1028 doi: 10.2337/diacare.27.5.1028.
  10. Weng J, Li Y, Xu W, Shi L, Zhang Q, Zhu D, et al. Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. The Lancet 2008;371(9626):1753-1760. Available from: http://linkinghub.elsevier.com/retrieve/pii/S014067360860762X PubMed PMID: 18502299. doi: 10.1016/S0140-6736(08)60762-X.
  11. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger PM. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetic Medicine 2012;29(5):682-689. Available from: http://doi.wiley.com/10.1111/j.1464-5491.2012.03605.x doi: 10.1111/j.1464-5491.2012.03605.x.
  12. Home P, Naggar NE, Khamseh M, Gonzalez-Galvez G, Shen C, Chakkarwar P, et al. An observational non-interventional study of people with diabetes beginning or changed to insulin analogue therapy in non-Western countries: the A1chieve study. Diabetes Res Clin Pract 2011;94(3):352-363. Available from: http://www.diseaseinfosearch.org/result/2236 PubMed PMID: 22153567. doi: 10.1016/j.diabres.2011.10.021.
  13. Meneghini LF, Dornhorst A, Sreenan S. Once-daily insulin detemir in a cohort of insulin-naïve patients with type 2 diabetes: a sub-analysis from the PREDICTIVE study. Curr Med Res Opin 2009;25(4):1029-1035. Available from: http://informahealthcare.com/doi/abs/10.1185/03007990902840871 doi: 10.1185/03007990902840871.
  14. Wang F, Carabino JM, Vergara CM. Insulin glargine: a systematic review of a long-acting insulin analogue. Clin Ther 2003;25(6):1541-1577. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=12860485 PubMed PMID: 12860485.
  15. Giugliano D, Maiorino MI, Bellastella G, Chiodini P, Esposito K. Multiple HbA1c targets and insulin analogues in type 2 diabetes: a systematic review. Journal of Diabetes and its Complications 2011;25(4):275-281. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1056872711000407 doi: 10.1016/j.jdiacomp.2011.03.005.
  16. Pennartz C, Schenker N, Menge BA, Schmidt WE, Nauck MA, Meier JJ. Chronic Reduction of Fasting Glycemia With Insulin Glargine Improves First- and Second-Phase Insulin Secretion in Patients With Type 2 Diabetes. Diabetes Care 2011;34(9):2048-2053. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc11-0471 PubMed PMID: 21775756. doi: 10.2337/dc11-0471.
  17. Meier JJ, Pennartz C, Schenker N, Menge BA, Schmidt WE, Heise T, et al. Hyperglycaemia is associated with impaired pulsatile insulin secretion: effect of basal insulin therapy. Diabetes Obes Metab 2013;15(3):258-263. Available from: http://doi.wiley.com/10.1111/dom.12022 PubMed PMID: 23039360. doi: 10.1111/dom.12022.
  18. Blonde L, Merilainen M, Karwe V, Raskin P. Patient-directed titration for achieving glycaemic goals using a once-daily basal insulin analogue: an assessment of two different fasting plasma glucose targets - the TITRATE TM study. Diabetes, Obesity and Metabolism 2009;11(6):623-631. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2009.01060.x PubMed PMID: 19515182. doi: 10.1111/j.1463-1326.2009.01060.x.
  19. Holman RR, Thorne KI, Farmer AJ, Davies MJ, Keenan JF, Paul S, et al. Addition of Biphasic, Prandial, or Basal Insulin to Oral Therapy in Type 2 Diabetes. N Engl J Med 2007;357(17):1716-1730. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa075392 PubMed PMID: 17890232. doi: 10.1056/NEJMoa075392.
  20. Garber AJ, Wahlen J, Wahl T, Bressler P, Braceras R, Allen E, et al. 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;8(1):58-66. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2005.00563.x PubMed PMID: 16367883. doi: 10.1111/j.1463-1326.2005.00563.x.
  21. Gumprecht J, Benroubi M, Borzi V, Kawamori R, Shaban J, Shah S. Intensification to biphasic insulin aspart 30/70 (BIAsp 30, NovoMix 30) can improve glycaemic control in patients treated with basal insulins: a subgroup analysis of the IMPROVE observational study. Int J Clin Pract. 2009;63(6):966-972. doi: 10.1111/j.1742-1241.2009.02064.x.
  22. Holman RR, Farmer AJ, DaviesMJ , et al. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009;361(18):1736-1747. doi: 10.1056/NEJMoa0905479.
  23. Giugliano D, Maiorino MI, Bellastella G, et al. Treatment regimens with insulin analogues and haemoglobin A1c target of < 7% in type 2 diabetes: a systematic review. Diabetes Res Clin Pract 2011;92:1-10
  24. Meneghini L, Mersebach H, Kumar S, Svendsen AL, Hermansen K. Comparison of 2 Intensification Regimens with Rapid-Acting Insulin Aspart in Type 2 Diabetes Mellitus Inadequately Controlled by Once-Daily Insulin Detemir and Oral Antidiabetes Drugs: The Step-Wise Randomized Study. Endocrine Practice 2011;17(5):727-736. Available from: http://aace.metapress.com/openurl.asp?genre=article&id=doi: 10.4158/EP10367.OR. PubMed PMID: 21550957. doi: 10.4158/EP10367.OR.
  25. Vijan S, Hayward RA, Ronis DL, Hofer TP. Brief report: the burden of diabetes therapy: implications for the design of effective patient-centered treatment regimens. J Gen Intern Med 2005;20(5):479-482. Available from: http://link.springer.com/10.1111/j.1525-1497.2005.0117.x PubMed PMID: 15963177. doi: 10.1111/j.1525-1497.2005.0117.x.
  26. Peyrot M, Rubin RR, Kruger DF, Travis LB. Correlates of Insulin Injection Omission. Diabetes Care 2010;33(2):240-245. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc09-1348 PubMed PMID: 20103556. doi: 10.2337/dc09-1348.
  27. Peyrot M, Barnett AH, Meneghini LF, Schumm-Draeger P. Factors associated with injection omission/non-adherence in the Global Attitudes of Patients and Physicians in Insulin Therapy study. Diabetes Obes Metab 2012;14(12):1081-1087. Available from: https://assays.cancer.gov/CPTAC-228 PubMed PMID: 22726104. doi: 10.1111/j.1463-1326.2012.01636.x.
  28. Davidson MB, Raskin P, Tanenberg RJ, Vlajnic A, Hollander P. A Stepwise Approach to Insulin Therapy in Patients with Type 2 Diabetes Mellitus and Basal Insulin Treatment Failure. Endocrine Practice 2011;17(3):395-403. Available from: http://aace.metapress.com/openurl.asp?genre=article&id=doi: 10.4158/EP10323.OR. PubMed PMID: 21324825. doi: 10.4158/EP10323.OR.
  29. Raccah D, Haak TJ, Huet D, Monnier L, Robertson D, Labard P, et al. Comparison of stepwise addition of prandial insulin to a basal-bolus regimen when basal insulin is insufficient for glycaemic control in type 2 diabetes: Results of the OSIRIS study. Diabetes & Metabolism 2012;38(6):507-514. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1262363612001577 doi: 10.1016/j.diabet.2012.08.010.
  30. Rodbard HW, Visco VE, Andersen H, Hiort LC, Shu DHW. Treatment intensification with stepwise addition of prandial insulin aspart boluses compared with full basal-bolus therapy (FullSTEP Study): a randomised, treat-to-target clinical trial. Lancet Diabetes Endocrinol 2014;2(1):30-37. doi: 10.1016/S2213-8587(13)70090-1.
  31. Jonassen I, Havelund S, Hoeg-Jensen T, Steensgaard DB, Wahlund P, Ribel U. Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin. Pharm Res 2012;29(8):2104-2114. Available from: http://link.springer.com/10.1007/s11095-012-0739-z PubMed PMID: 22485010. doi: 10.1007/s11095-012-0739-z.
  32. Jonassen I, Hoeg-Jensen T, Havelund S, Ribel U. Ultra-long acting insulin degludec can be combined with rapid-acting insulin aspart in a soluble co-formulation (Abstract). J Pept Sci 2010;16:32.
  33. Heise T, Nosek L, Bøttcher SG, Hastrup H, Haahr H. Ultra-long-acting insulin degludec has a flat and stable glucose-lowering effect in type 2 diabetes. Diabetes Obes Metab 2012;14(10):944-950. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2012.01638.x doi: 10.1111/j.1463-1326.2012.01638.x.
  34. Heise T, Nosek L, Hastrup H, et al. IDegAsp shows distinct prandial and basal glucose-lowering effects at steady state in subjects with type 1 diabetes (abstract 926-P). Diabetes 2013;62(suppl 1):235.
  35. Heise T, Nosek L, Roepstorff C, Chenji S, Klein O, Haahr H. Distinct Prandial and Basal Glucose-Lowering Effects of Insulin Degludec/Insulin Aspart (IDegAsp) at Steady State in Subjects with Type 1 Diabetes Mellitus. Diabetes Ther 2014;5(1):255-265. Available from: http://link.springer.com/10.1007/s13300-014-0070-2 doi: 10.1007/s13300-014-0070-2.
  36. Nosek L, Heise T, Klein O, Coester HV, Roepstorff C, Svendsen A, et al. IDegAsp produces a dose-proportional glucose-lowering effect in subjects with type 1 diabetes - PS1041. Diabetologia 2013;56(suppl 1).
  37. Jonassen I, Havelund S, Ribel U et al. Insulin degludec is a new generation ultra-long acting basal insulin with a unique mechanism of protraction based on multi-hexamer formation. Diabetes 2010;59(Suppl 1):A11
  38. Heise T, Hermanski L, Nosek L, Feldman A, Rasmussen S, Haahr H. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab 2012;14(9):859-864. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2012.01627.x PubMed PMID: 22594461. doi: 10.1111/j.1463-1326.2012.01627.x.
  39. Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, Liebl A, et al. A New-Generation Ultra-Long-Acting Basal Insulin With a Bolus Boost Compared With Insulin Glargine in Insulin-Naive People With Type 2 Diabetes: A randomized, controlled trial. Diabetes Care 2011;34(3):669-674. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc10-1905 PubMed PMID: 21285389. doi: 10.2337/dc10-1905.
  40. Niskanen L, Leiter LA, Franek E, Weng J, Damci T, Muñoz-Torres M, et al. Comparison of a soluble co-formulation of insulin degludec/insulin aspart vs biphasic insulin aspart 30 in type 2 diabetes: a randomised trial. Eur J Endocrinol 2012;167(2):287-294. Available from: http://eje-online.org/cgi/pmidlookup?view=long&pmid=22660026 PubMed PMID: 22660026. doi: 10.1530/EJE-12-0293.
  41. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) . Guidance for Industry: Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention (Draft guidance). 2013. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071624.pdf
  42. Franek E, Haluzík M, Varžić SC et al. IDegAsp provides superior FPG control and reduced hypoglycaemia vs BIAsp 30 in insulin-naive adults with type 2 diabetes: a randomised phase 3 trial. Diabetologia 2014; 57(Suppl1):S380
  43. Heise T, Tack CJ, Cuddihy R, Davidson J, Gouet D, Liebl A, et al. A New-Generation Ultra-Long-Acting Basal Insulin With a Bolus Boost Compared With Insulin Glargine in Insulin-Naive People With Type 2 Diabetes: A randomized, controlled trial. Diabetes Care 2011;34(3):669-674. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc10-1905 PubMed PMID: 21285389. doi: 10.2337/dc10-1905.
  44. Fulcher GR, Christiansen JS, Bantwal G, Polaszewska-Muszynska M, Mersebach H, Andersen TH, et al. Comparison of insulin degludec/insulin aspart and biphasic insulin aspart 30 in uncontrolled, insulin-treated type 2 diabetes: a phase 3a, randomized, treat-to-target trial. Diabetes Care;37(8):2084-2090. doi: 10.2337/dc13-2908.
  45. Hirsch IB, Bode B, Courreges JP, Dykiel P, Franek E, Hermansen K, et al. Insulin Degludec/Insulin Aspart Administered Once Daily at Any Meal, With Insulin Aspart at Other Meals Versus a Standard Basal-Bolus Regimen in Patients With Type 1 Diabetes: A 26-week, phase 3, randomized, open-label, treat-to-target trial. Diabetes Care 2012;35(11):2174-2181. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc11-2503 PubMed PMID: 22933438. doi: 10.2337/dc11-2503.
  46. Onishi Y, Ono Y, Rabøl R, Endahl L, Nakamura S. Superior glycaemic control with once-daily insulin degludec/insulin aspart versus insulin glargine in Japanese adults with type 2 diabetes inadequately controlled with oral drugs: a randomized, controlled phase 3 trial. Diabetes Obes Metab 2013;15(9):826-832. Available from: http://doi.wiley.com/10.1111/dom.12097 PubMed PMID: 23557077. doi: 10.1111/dom.12097.
  47. Vaag A, Christiansen JS, Niskanen L, Rasmussen S et al. Lower rates of overall, nocturnal and severe hypoglycaemia during maintenance treatment with IDegAsp vs biphasic insulin aspart 30 in patients with type 2 diabetes mellitus: a meta-analysis. Diabetologia 2013;56(Suppl.1):S83
  48. UK Hypoglycaemia Study Group . Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50(6):1140-1147. Available from: http://link.springer.com/10.1007/s00125-007-0599-y doi: 10.1007/s00125-007-0599-y.
  49. Liebl A, Davidson J, Mersebach H, Dykiel P, Tack CJ, Heise T. A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: results from continuous glucose monitoring in a proof-of-concept trial. J Diabetes Sci Technol 2013;7(5):1328-1336.
  50. Vaag A, Christiansen JS, Niskanen L, Johansen T et al. IDegAsp lowers the rate of hypoglycaemia vs biphasic insulin aspart 30 in adults with type 2 diabetes achieving glycaemic target (HbA1c <7.0%): a meta-analysis. Diabetologia (2014) 57(Suppl1):S400
  51. Laakso M. Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention. J Intern Med 2001;249(3):225-235. Available from: http://doi.wiley.com/10.1046/j.1365-2796.2001.00789.x PubMed PMID: 11285042. doi: 10.1046/j.1365-2796.2001.00789.x.
  52. The Action to Control Cardiovascular Risk in Diabetes Study Group . The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of Intensive Glucose Lowering in Type 2. Diabetes (ACCORD Study). N Engl J Med 2008;358:2545-2559.
  53. The ADVANCE Collaborative Group . Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2008;358(24):2560-2572. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0802987 doi: 10.1056/NEJMoa0802987.
  54. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes. N Engl J Med 2009;360(2):129-139. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0808431 PubMed PMID: 19092145. doi: 10.1056/NEJMoa0808431.
  55. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) . Guidance for Industry Diabetes Mellitus — Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes. 2008. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
  56. Hirshberg B, Raz I. Impact of the U.S. Food and Drug Administration cardiovascular assessment requirements on the development of novel antidiabetes drugs. Diabetes Care 2011;34(Suppl2):101-106. doi: 10.2337/dc11-s202.
  57. Endocrinologic and Metabolic Drugs Advisory Committee Meeting . NDA 203313 and NDA 203314 Insulin Degludec and Insulin Degludec/Aspart. 2012. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM327015.pdf
  58. Moghissi E, King AB. Individualizing Insulin Therapy in the Management of Type 2 Diabetes. The American Journal of Medicine. 2014; 127(10): S3-10. doi: 10.1016/j.amjmed.2014.07.002.

Views

Abstract - 2190

PDF (Russian) - 2008

PlumX


Copyright (c) 2014 Dedov I.I., Shestakova M.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.