Insulin degludec is a new ultra-long-acting insulin analogue
https://doi.org/10.14341/DM2014291-104
Abstract
Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba?) is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more) non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.
About the Authors
Ivan Ivanovich Dedov
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, professor, fellow of Russian Academy of Sciences, Head of Endocrinology Research Centre
Russian Federation
MD, PhD, professor, fellow of Russian Academy of Sciences, Head of Endocrinology Research Centre
Marina Vladimirovna Shestakova
Endocrinology Research Centre, Moscow
Russian Federation
MD, PhD, professor, corresponding fellow of Russian Academy of Sciences, Head of Diabetes Institution in Endocrinology Research Centre
Russian Federation
MD, PhD, professor, corresponding fellow of Russian Academy of Sciences, Head of Diabetes Institution in Endocrinology Research Centre
References
1. Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, et al. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32(1):193-203. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc08-9025 doi: 10.2337/dc08-9025.
2. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA 1999;281(21):2005-2012. Available from: http://ClinicalTrials.gov/search/term=10359389%20%5BPUBMED-IDS%5D PubMed PMID: 10359389.
3. UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33. The Lancet 1998;352(9131):837-853. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673698070196 doi: 10.1016/S0140-6736(98)07019-6.
4. 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 doi: 10.1136/bmj.321.7258.405.
5. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-Year Follow-up of Intensive Glucose Control in Type 2 Diabetes. N Engl J Med 2008;359(15):1577-1589. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0806470 doi: 10.1056/NEJMoa0806470.
6. 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.
7. Randlov J, Poulsen JU. How much do forgotten insulin injections matter to hemoglobin a1c in people with diabetes? A simulation study. Journal of Diabetes Science and Technology 2008;2(2):229-235. Available from: http://dst.sagepub.com/lookup/doi/10.1177/193229680800200209 PubMed PMID: 19885347. doi: 10.1177/193229680800200209.
8. Balkrishnan R, Rajagopalan R, Camacho FT, Huston SA, Murray FT, Anderson RT. Predictors of medication adherence and associated health care costs in an older population with type 2 diabetes mellitus: A longitudinal cohort study. Clinical Therapeutics 2003;25(11):2958-2971. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0149291803803478 doi: 10.1016/S0149-2918(03)80347-8.
9. 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.
10. 10. Giugliano D, Maiorino MI, Bellastela 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):1-10. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0168822710003967 doi: 10.1016/j.diabres.2010.08.006
11. Heise T, Pieber TR. Towards peakless, reproducible and long-acting insulins. An assessment of the basal analogues based on isoglycaemic clamp studies. Diabetes Obes Metab 2007;9(5):648-659. Available from: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1463-1326.2007.00756.x PubMed PMID: 17645556. doi: 10.1111/j.1463-1326.2007.00756.x.
12. Klein O, Lynge J, Endahl L, Damholt B, Nosek L, Heise T. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes. Diabetes Obes Metab 2007;9(3):290-299. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2006.00685.x PubMed PMID: 17391154. doi: 10.1111/j.1463-1326.2006.00685.x.
13. Russell-Jones D, Simpson R, Hylleberg B, Draeger E, Bolinder J. Effects of QD insulin detemir or neutral protamine Hagedorn on blood glucose control in patients with type I diabetes mellitus using a basal-bolus regimen. Clinical Therapeutics 2004;26(5):724-736. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0149291804900720 doi: 10.1016/S0149-2918(04)90072-0.
14. Heise T, Nosek L, Ronn BB, Endahl L, Heinemann L, Kapitza C, et al. Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in People With Type 1 Diabetes. Diabetes 2004;53(6):1614-1620. Available from: http://diabetes.diabetesjournals.org/cgi/doi/10.2337/diabetes.53.6.1614 doi: 10.2337/diabetes.53.6.1614.
15. Hermansen K. 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;29(6):1269-1274. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc05-1365 doi: 10.2337/dc05-1365.
16. Rosenstock J, Davies M, Home PD, Larsen J, Koenen C, Schernthaner G. A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetologia 2008;51(3):408-416. Available from: http://link.springer.com/10.1007/s00125-007-0911-x doi: 10.1007/s00125-007-0911-x.
17. DeVries JH, Nattrass M, Pieber TR. Refining basal insulin therapy: what have we learned in the age of analogues. Diabetes Metab. Res. Rev 2007;23(6):441-454. Available from: http://doi.wiley.com/10.1002/dmrr.762 doi: 10.1002/dmrr.762.
18. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues vs. NPH human insulin in type 1 diabetes. A meta-analysis. Diabetes, Obesity and Metabolism 2009;11(4):372-378. Available from: http://doi.wiley.com/10.1111/j.1463-1326.2008.00976.x doi: 10.1111/j.1463-1326.2008.00976.x.
19. Monami M, Marchionni N, Mannucci E. Long-acting insulin analogues versus NPH human insulin in type 2 diabetes: a meta-analysis. Diabetes Research and Clinical Practice 2008;81(2):184-189. Available from: http://linkinghub.elsevier.com/retrieve/pii/S016882270800185X doi: 10.1016/j.diabres.2008.04.007.
20. Brod M, Barnett AH, Rana A, Peyrot Mark. GAPP2™: Global Survey Finds in the last month one in four Type 2 diabetes patients do not take basal insulin as prescribed and over a third suffer hypoglycaemia. Diabetes 2012;61(Suppl.1A):LB7.
21. Brod M, Christensen T, Thomsen TL, Bushnell DM. The Impact of Non-Severe Hypoglycemic Events on Work Productivity and Diabetes Management. Value in Health 2011;14(5):665-671. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1098301511001331 doi: 10.1016/j.jval.2011.02.001.
22. Wild D, von Maltzahn R, Brohan E, Christensen T, Clauson P, Gonder-Frederick L. A critical review of the literature on fear of hypoglycemia in diabetes: Implications for diabetes management and patient education. Patient Education and Counseling 2007;68(1):10-15. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0738399107001760 doi: 10.1016/j.pec.2007.05.003.
23. Nishimura E, Sørensen AR, Hansen BF, et al. Insulin degludec: a new ultra-long, basal insulin designed to maintain full metabolic effect while minimizing mitogenic potential. Diabetologia 2010;53(Suppl.1):388-389.
24. 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 doi: 10.1007/s11095-012-0739-z.
25. Heise T, Hövelmann U, Nosek L, Bøttcher SG, Granhall C, Haahr H. Insulin degludec has a two-fold longer half-life and a more consistent pharmacokinetic profile than insulin glargine. In: Abstracts of the 47th Annual Meeting of the EASD, Lisbon 2011. Diabetologia 2011;54(Suppl 1):425.
26. Kurtzhals P, Heise T, Strauss HM, Bøttcher SG, Granhall C, Haahr H, et al. Multi-hexamer formation is the underlying basis for the ultra-long glucose-lowering effect of insulin degludec. In: Abstracts of the 47th Annual Meeting of the EASD, Lisbon 2011. Diabetologia 2011;54(Suppl 1):426.
27. 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.
28. Koehler G, Treiber G, Wutte A, Korsatko S, Mader JK, Semlitsch B, et al. Pharmacodynamics of the long-acting insulin analogues detemir and glargine following single-doses and under steady-state conditions in patients with type 1 diabetes. Diabetes Obes Metab 2014;16(1):57-62. Available from: http://doi.wiley.com/10.1111/dom.12178 doi: 10.1111/dom.12178.
29. 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 doi: 10.1111/j.1463-1326.2012.01627.x.
30. US Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) . Guidance for Industry: Diabetes Mellitus: Develop-ing Drugs and Therapeutic Biologics for Treatment and Prevention (Draft guidance). Clinical/Medical; 2008. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071624.pdf
31. Zinman B, Philis-Tsimikas A, Cariou B, Handelsman Y, Rodbard HW, Johansen T, et al. Insulin Degludec Versus Insulin Glargine in Insulin-Naive Patients With Type 2 Diabetes: A 1-year, randomized, treat-to-target trial (BEGIN Once Long. Diabetes Care 2012;35(12):2464-2471. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc12-1205 doi: 10.2337/dc12-1205.
32. Garber AJ, King AB, Prato SD, Sreenan S, Balci MK, Muñoz-Torres M, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. The Lancet 2012;379(9825):1498-1507. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673612602050 doi: 10.1016/S0140-6736(12)60205-0.
33. Heller S, Buse J, Fisher M, Garg S, Marre M, Merker L, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial. The Lancet 2012;379(9825):1489-1497. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0140673612602049 doi: 10.1016/S0140-6736(12)60204-9.
34. Meneghini L, Atkin SL, Gough SCL, Raz I, Blonde L, Shestakova M, et al. The Efficacy and Safety of Insulin Degludec Given in Variable Once-Daily Dosing Intervals Compared With Insulin Glargine and Insulin Degludec Dosed at the Same Time Daily: A 26-week, randomized, open-label, parallel-group, treat-to-target trial in individuals with type 2 diabetes. Diabetes Care 2013;36(4):858-864. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc12-1668 doi: 10.2337/dc12-1668.
35. Mathieu C, Hollander P, Miranda-Palma B, Cooper J, Franek E, Russell-Jones D, et al. Efficacy and Safety of Insulin Degludec in a Flexible Dosing Regimen vs Insulin Glargine in Patients With Type 1 Diabetes (BEGIN: Flex T1): A 26-Week Randomized, Treat-to-Target Trial With a 26-Week Extension. The Journal of Clinical Endocrinology & Metabolism 2013;98(3):1154-1162. Available from: http://press.endocrine.org/doi/abs/10.1210/jc.2012-3249 doi: 10.1210/jc.2012-3249.
36. Onishi Y, Iwamoto Y, Yoo SJ, Clauson P, Tamer SC, Park S. Insulin degludec compared with insulin glargine in insulin-naïve patients with type 2 diabetes: A 26-week, randomized, controlled, Pan-Asian, treat-to-target trial. J Diabetes Invest 2013;4(6):605-612. Available from: http://doi.wiley.com/10.1111/jdi.12102 doi: 10.1111/jdi.12102.
37. Gough SCL, Bhargava A, Jain R, Mersebach H, Rasmussen S, Bergenstal RM. Low-Volume Insulin Degludec 200 Units/mL Once Daily Improves Glycemic Control Similarly to Insulin Glargine With a Low Risk of Hypoglycemia in Insulin-Naive Patients With Type 2 Diabetes: A 26-week, randomized, controlled, multinational, treat-to-target trial: The BEGIN LOW VOLUME trial. Diabetes Care 2013;36(9):2536-2542. Available from: http://care.diabetesjournals.org/cgi/doi/10.2337/dc12-2329 doi: 10.2337/dc12-2329.
38. Akram K, Pedersen-Bjergaard U, Carstensen B, Borch-Johnsen K, Thorsteinsson B. Frequency and risk factors of severe hypoglycaemia in insulin-treated Type 2 diabetes: a cross-sectional survey. Diabetic Med 2006;23(7):750-756. Available from: http://doi.wiley.com/10.1111/j.1464-5491.2006.01880.x doi: 10.1111/j.1464-5491.2006.01880.x.
39. Holman RR, Farmer AJ, Davies MJ, Levy JC, Darbyshire JL, Keenan JF, et al. Three-Year Efficacy of Complex Insulin Regimens in Type 2 Diabetes. N Engl J Med 2009;361(18):1736-1747. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0905479 doi: 10.1056/NEJMoa0905479.
40. Ratner RE, Gough SCL, Mathieu C, Del Prato S, Bode B, Mersebach H, et al. Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials. Diabetes Obes Metab 2012;15(2):175-184. Available from: http://dx.doi.org/10.1111/dom.12032 PubMed PMID: 23130654. doi: 10.1111/dom.12032.
41. Rodbard HW, Cariou B, Zinman B, Handelsman Y, Philis-Tsimikas A, Skjøth TV, et al. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes: a 2-year randomized, treat-to-target trial. Diabet Med 2013;30(11):1298-1304. Available from: http://ClinicalTrials.gov/search/term=23952326%20%5BPUBMED-IDS%5D PubMed PMID: 23952326. doi: 10.1111/dme.12303.
42. Bode BW, Buse JB, Fisher M, Garg SK, Marre M, Merker L, et al. Insulin degludec improves glycaemic control with lower nocturnal hypoglycaemia risk than insulin glargine in basal-bolus treatment with mealtime insulin aspart in Type 1 diabetes (BEGIN ® Basal-Bolus Type 1): 2-year results of a randomized clinical trial. Diabet. Med 2013;30(11):1293-1297. Available from: http://doi.wiley.com/10.1111/dme.12243 doi: 10.1111/dme.12243.
43. Hollander P, Vora J, Niemeyer M, Johansen T, Bergenstal R. Insulin degludec does not in-crease antibody formation compared to insulin glargine: an evaluation of phase 3a trials. J Diab Invest 2012;3(Suppl.1):176(Abstract PCS-04-3).
44. Laakso M. Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention. Journal of Internal Medicine 2008;249(3):225-235. Available from: http://doi.wiley.com/10.1111/j.1365-2796.2001.00789.x doi: 10.1111/j.1365-2796.2001.00789.x.
45. Effects of Intensive Glucose Lowering in Type 2 Diabetes. N Engl J Med 2008;358(24):2545-2559. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa0802743 doi: 10.1056/NEJMoa0802743.
46. 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.
47. 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 doi: 10.1056/NEJMoa0808431.
48. 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. Clinical/Medical; 2008. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm071627.pdf
49. Committee for Medicinal Products for Human Use (CHMP) . Guideline on clinical investigation of medicinal products in the treatment or prevention of diabetes mellitus. European medicines agency; 2012. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2012/06/WC500129256.pdf
50. Endocrinologic and Metabolic Drugs Advisory Committee Meeting . FDA briefing document: NDA 203313 and NDA 203314 (insulin degludec and insulin degludec/insulin aspart. http: //www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM327015.pdf. 2012.
51. Peyrot M, Rubin RR, Khunti K. Addressing barriers to initiation of insulin in patients with type 2 diabetes. Prim Care Diabetes 2010;4(Suppl 1):11-18. Available from: http://www.scholaruniverse.com/ncbi-linkout?id=20394886 PubMed PMID: 20394886. doi: 10.1016/S1751-9918(10)60004-6.
52. Polonsky WH, Fisher L, Guzman S, Villa-Caballero L, Edelman SV. Psychological insulin resistance in patients with type 2 diabetes: the scope of the problem. Diabetes Care 2005;28(10):2543-2545. Available from: http://www.nlm.nih.gov/medlineplus/diabetesmedicines.html PubMed PMID: 16186296.
53. Rubin RR, Peyrot M. Psychological issues and treatments for people with diabetes. J. Clin. Psychol 2001;57(4):457-478. Available from: http://doi.wiley.com/10.1002/jclp.1041 PubMed PMID: 11255202. doi: 10.1002/jclp.1041.
54. Freemantle N, Meneghini L, Christensen T, Wolden ML, Jendle J, Ratner R. Insulin degludec improves health-related quality of life (SF-36 ® ) compared with insulin glargine in people with Type 2 diabetes starting on basal insulin: a meta-analysis of phase 3a trials. Diabet. Med;30(2):226-232. Available from: http://doi.wiley.com/10.1111/dme.12086 doi: 10.1111/dme.12086.
55. Freemantle N, Evans M, Christensen T, Wolden ML, Bjorner JB. A comparison of health-related quality of life (health utility) between insulin degludec and insulin glargine: a meta-analysis of phase 3 trials. Diabetes Obes Metab 2013;15(6):564-571. Available from: http://doi.wiley.com/10.1111/dom.12086 doi: 10.1111/dom.12086.
56. Rodbard H, Cariou B, Zinman B, Handelsman Y, Wolden M, Rana A, et al. Health status and hypoglycemia with insulin degludec versus insulin glargine: a 2-year trial in insu-lin-naïve patients with Type 2 diabetes. Diabetes Obes Metab 2014. doi: 10.1111/dom.12271.
57. Home PD, Meneghini L, Wendisch U, Ratner RE, Johansen T, Christensen TE, et al. Improved health status with insulin degludec compared with insulin glargine in people with Type 1 diabetes. Diabetic Medicine 2011;29(6):716-720. Available from: http://doi.wiley.com/10.1111/j.1464-5491.2011.03547.x doi: 10.1111/j.1464-5491.2011.03547.x.
58. Philis-Tsimikas A, Brod M, Niemeyer M, Ocampo Francisco AM, Rothman J. Insulin degludec once-daily in type 2 diabetes: simple or step-wise titration (BEGIN: once simple use). Adv Ther 2013;30(6):607-622. Available from: http://europepmc.org/abstract/MED/23812875 PubMed PMID: 23812875. doi: 10.1007/s12325-013-0036-1.
59. 59. Алгоритмы специализированной медицинской помощи больным сахарным диабетом. Под редакцией И.И. Дедова, М.В. Шестаковой (6-й выпуск). Сахарный диабет. 2013;(1s):1-121. [Dedov I, Shestakova M, Aleksandrov A, Galstyan G, Grigoryan O, Esayan R, et al. Standards of specialized diabetes care. Edited by Dedov II, Shestakova MV (6th edition). Diabetes mellitus. 2013;(1S):1-120.] doi: http://dx.doi.org/10.14341/DM20131S1-121
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Dedov I.I., Shestakova M.V. Insulin degludec is a new ultra-long-acting insulin analogue. Diabetes mellitus. 2014;17(2):91-104. https://doi.org/10.14341/DM2014291-104
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