Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naïve or insulin-naïve patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal–bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%–50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.

1. Institute for Public Health. (2020). National Health and Morbidity Survey (NHMS) 2019: Non-communicable diseases, healthcare demand, and health literacy—Key findings. Ministry of Health Malaysia. https://iptk.moh.gov.my/images/technical_report/2020/4_Infographic_Booklet_NHMS_2019_-_English.pdf
2. Ministry of Health Malaysia. (2020). National Diabetes Registry report 2013–2019. Ministry of Health Malaysia. https://www.moh.gov.my/moh/resources/Penerbitan/Rujukan/NCD/Diabetes/National_Diabetes_Registry_Report_2013-2019_26082021.pdf
3. Zanariah, H., Foo, S. H., & Lim, S. C. (2011). Practical guide to insulin therapy in type 2 diabetes mellitus. Malaysian Endocrine & Metabolic Society.
4. Chun, J., Strong, J., & Urquhart, S. (2019). Insulin initiation and titration in patients with type 2 diabetes. Diabetes Spectrum, 32(2), 104–111. https://doi.org/10.2337/ds18-0005
5. Havelund, S., Ribel, U., Hubálek, F., Hoeg-Jensen, T., Wahlund, P. O., & Jonassen, I. (2015). Investigation of the physico-chemical properties that enable co-formulation of basal insulin degludec with fast-acting insulin aspart. Pharmaceutical Research, 32(7), 2250–2258. https://doi.org/10.1007/s11095-014-1614-x
6. Haahr, H., Fita, E. G., & Heise, T. (2017). A review of insulin degludec/insulin aspart: Pharmacokinetic and pharmacodynamic properties and their implications in clinical use. Clinical Pharmacokinetics, 56(4), 339–354. https://doi.org/10.1007/s40262-016-0455-7
7. Hirsch, I. B., Bode, B., Courreges, J. P., Dykiel, P., Franek, E., Hermansen, K., King, A. B., Mersebach H., & BOOST T1 Study Group. (2012). 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, 35(11), 2174–2181. https://doi.org/10.2337/dc11-2503
8. Hirsch, I. B., Franek, E., Mersebach, H., Bardtrum, L., & Hermansen, K. (2017). Safety and efficacy of insulin degludec/insulin aspart with bolus mealtime insulin aspart compared with standard basal-bolus treatment in people with type 1 diabetes: 1-year results from a randomized clinical trial (BOOST® T1). Diabetic Medicine, 34(2), 167–173. https://doi.org/10.1111/dme.13068
9. Onishi, Y., Ono, Y., Rabøl, R., Endahl, L., & Nakamura, S. (2013). 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, Obesity and Metabolism, 15(9), 826–832. https://doi.org/10.1111/dom.12097
10. Gupta, Y., Astamirova, K., Fita, E., & Demir, T. (2018). Similar glycaemic control and less nocturnal hypoglycaemia with intensification of IDegAsp QD or BID vs glargine U100 QD + IAsp 1-3 in adults with type 2 diabetes. In Y. Gupta, K. Astamirova, E. Fita, & T. Demir (Eds.), 54th Annual Meeting of the European Association for the Study of Diabetes (p. e836). Berlin, Germany.
11. Franek, E., Haluzík, M., Canecki Varžić, S., Smahelová, A., Sargin, M., Rondoom, K., Endahl, L., & Christiansen, J. S. (2016). Twice-daily insulin degludec/insulin aspart provides superior fasting plasma glucose control and a reduced rate of hypoglycaemia compared with biphasic insulin aspart 30 in insulin-naïve adults with type 2 diabetes. Diabetic Medicine, 33(4), 497–505. https://doi.org/10.1111/dme.12982
12. Fulcher, G. R., Christiansen, J. S., Bantwal, G., Polaszewska-Muszynska, M., Mersebach, H., Andersen, T. H., Niskanen, L., & BOOST: Intensify Premix I Investigators. (2014). 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. https://doi.org/10.2337/dc13-2908
13. Kaneko, S., Chow, F., Choi, D. S., Tan, E. C., Deerochanawong, C., Jin, J., & BOOST: Intensify All Trial Investigators. (2015). Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: A 26-week, randomised, treat-to-target trial. Diabetes Research and Clinical Practice, 107(1), 139–147. https://doi.org/10.1016/j.diabres.2014.09.026
14. Yang, W., Ma, J., Hong, T., Liu, M., Miao, H., Peng, Y., Zhang, J., Bardtrum, L., & Macura, S. (2019). Efficacy and safety of insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Chinese adults with type 2 diabetes: A phase III, open-label, 2:1 randomized, treat-to-target trial. Diabetes, Obesity and Metabolism, 21(7), 1652–1660. https://doi.org/10.1111/dom.13703
15. Rodbard, H. W., Cariou, B., Pieber, T. R., Endahl, L. A., Zacho, J., & Cooper, J. G. (2016). Treatment intensification with an insulin degludec (IDeg)/insulin aspart (IAsp) co-formulation twice daily compared with basal IDeg and prandial IAsp in type 2 diabetes: A randomized, controlled phase III trial. Diabetes, Obesity and Metabolism, 18(3), 274–280. https://doi.org/10.1111/dom.12609
16. Hassanein, M., Echtay, A. S., Malek, R., Omar, M., Shaltout, I., El-Naggar, N., Mersebach, H., & Al Maatouq, M. (2018). Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan. Diabetes Research and Clinical Practice, 135, 218–226. https://doi.org/10.1016/j.diabres.2017.11.027
17. Kaneko, S., da Rocha Fernandes, J. D., Yamamoto, Y., Langer, J., & Faurby, M. (2021). A Japanese study assessing glycemic control with use of IDegAsp co-formulation in patients with type 2 diabetes in clinical practice: The JAGUAR study. Advances in Therapy, 38(3), 1638–1649. https://doi.org/10.1007/s12325-021-01623-y
18. Özçelik, S., Çelik, M., Vural, A., Aydın, B., Özçelik, M., & Gozu, H. (2020). Outcomes of transition from premixed and intensive insulin therapies to insulin aspart/degludec co-formulation in type 2 diabetes mellitus: A real-world experience. Archives of Medical Science, 17(1), 1–8. https://doi.org/10.5114/aoms.2020.93264
19. Fulcher, G. R., Akhtar, S., Al-Jaser, S. J., El-Haddad, M., El-Hefnawy, M., El-Toomy, M., & Real-world IDegAsp Investigators. (2022). Initiating or switching to insulin degludec/insulin aspart in adults with type 2 diabetes: A real-world, prospective, non-interventional study across six countries. Advances in Therapy, 39(8), 3735–3748. https://doi.org/10.1007/s12325-022-02212-3
20. Ministry of Health Malaysia. (2020). Clinical practice guidelines: Management of type 2 diabetes mellitus (6th ed.). Ministry of Health Malaysia. https://www.moh.gov.my/moh/resources/Penerbitan/CPG/Endocrine/QR_T2DM_6th_Edition_QR_Guide_Digital.pdf
21. Weng, J. (2017). Short-term intensive insulin therapy could be the preferred option for new-onset type 2 diabetes mellitus patients with HbA1c > 9%. Journal of Diabetes, 9(10), 890–893. https://doi.org/10.1111/1753-0407.12581
22. Hanefeld, M. (2014). Use of insulin in type 2 diabetes: What we learned from recent clinical trials on the benefits of early insulin initiation. Diabetes & Metabolism, 40(6), 391–399. https://doi.org/10.1016/j.diabet.2014.08.006
23. Meneghini, L. F. (2009). Early insulin treatment in type 2 diabetes: What are the pros? Diabetes Care, 32(Suppl. 2), S266–S269. https://doi.org/10.2337/dc09-S32
24. Weng, J., Li, Y., Xu, W., Shi, L., Zhang, Q., Zhu, D., Lou, J., Zhou, Z., & Parallel-group Trial Investigators. (2008). Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: A multicentre randomised parallel-group trial. The Lancet, 371(9626), 1753–1760. https://doi.org/10.1016/S0140-6736(08)60762-X
25. Philis-Tsimikas, A., Astamirova, K., Gupta, Y., Guler, S., Demir, T., Langer, J., & Hansen, C. T. (2019). Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Research and Clinical Practice, 147, 157–165. https://doi.org/10.1016/j.diabres.2018.10.024
26. Zinman, B., Marso, S. P., Poulter, N. R., Emerson, S. S., Pieber, T. R., Pratley, R. E., Haahr, H., Lange, M., Brown-Frandsen, K., Moses, A., & DEVOTE Study Group. (2018). Day-to-day fasting glycaemic variability in DEVOTE: Associations with severe hypoglycaemia and cardiovascular outcomes (DEVOTE 2). Diabetologia, 61(1), 48–57. https://doi.org/10.1007/s00125-017-4423-z
27. McCoy, R. G., Van Houten, H. K., Ziegenfuss, J. Y., Shah, N. D., Wermers, R. A., & Smith, S. A. (2012). Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care, 35(9), 1897–1901. https://doi.org/10.2337/dc11-2054
28. Marso, S. P., McGuire, D. K., Zinman, B., Poulter, N. R., Emerson, S. S., Pieber, T. R., Pratley, R. E., Haahr, H., Lange, M., Brown-Frandsen, K., Moses, A., Skibsted, S., & DEVOTE Study Group. (2017). Efficacy and safety of degludec versus glargine in type 2 diabetes. New England Journal of Medicine, 377(8), 723–732. https://doi.org/10.1056/NEJMoa161569
29. Foley, R. N., Murray, A. M., Li, S., Herzog, C. A., McBean, A. M., Eggers, P. W., & Collins, A. J. (2005). Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. Journal of the American Society of Nephrology, 16(2), 489–495. https://doi.org/10.1681/ASN.2004030203
30. Moen, M. F., Zhan, M., Hsu, V. D., Walker, L. D., Einhorn, L. M., Seliger, S. L., & Fink, J. C. (2009). Frequency of hypoglycemia and its significance in chronic kidney disease. Clinical Journal of the American Society of Nephrology, 4(6), 1121–1127. https://doi.org/10.2215/CJN.00800209
31. Văduva, C., Popa, S., Moța, M., & Moța, E. (2013). Analysis of chronic kidney disease–associated glycemic variability in patients with type 2 diabetes using continuous glucose monitoring system. Romanian Journal of Diabetes Nutrition and Metabolic Diseases, 20(3), 315–322. https://doi.org/10.2478/rjdnmd-2014-0030
32. Al-Arouj, M., Assaad-Khalil, S., Buse, J., Fahdil, I., Fahmy, M., Hafez, S., Hassanein, M., Ibrahim, M. A., Kendall, D., Kishawi, S., Al-Madani, A., Mishriky, B. M., Al-Nakhi, A., & Vasan, S. (2010). Recommendations for management of diabetes during Ramadan: Update 2010. Diabetes Care, 33(8), 1895–1902. https://doi.org/10.2337/dc10-0896
33. Franz, M. J., Boucher, J. L., & Evert, A. B. (2014). Evidence-based diabetes nutrition therapy recommendations are effective: The key is individualization. Diabetes, Metabolic Syndrome and Obesity, 7, 65–72. https://doi.org/10.2147/DMSO.S45140
34. Seidelmann, S. B., Claggett, B., Cheng, S., Henglin, M., Shah, A., Steffen, L. M., Folsom, A. R., Rimm, E. B., Willett, W. C., & Solomon, S. D. (2018). Dietary carbohydrate intake and mortality: A prospective cohort study and meta-analysis. The Lancet Public Health, 3(9), e419–e428. https://doi.org/10.1016/S2468-2667(18)30135-X