Long-Term Safety and Clinical Outcomes with Insulin Degludec/Insulin Aspart Treatment in Japanese Patients with Diabetes: A Real-World, Prospective, Observational Study

Takuyuki Katabami, Kirsten T Eriksen, Yuiko Yamamoto, Yasushi Ishigaki, Takuyuki Katabami, Kirsten T Eriksen, Yuiko Yamamoto, Yasushi Ishigaki

Abstract

Introduction: Insulin degludec/insulin aspart (IDegAsp) provides effective glycaemic control with an acceptable safety profile in Japanese patients with diabetes in randomised clinical trials. This post-marketing surveillance study assessed long-term safety and clinical outcomes with IDegAsp in a Japanese real-world setting.

Methods: Multicentre, prospective, observational, open-label, single-arm study of Japanese patients with diabetes requiring insulin therapy, who had switched to IDegAsp at their treating physician's discretion in clinical practice. One year after initiating IDegAsp, incidence of adverse events (AEs [primary endpoint]), serious AEs, adverse drug reactions (ADRs), and severe hypoglycaemia (secondary safety endpoints) were assessed in the safety analysis set (SAS). Secondary effectiveness endpoints were change from baseline in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) in the effectiveness analysis set (EAS).

Results: Overall, 1321 patients were included (SAS, n = 1321; EAS, n = 1285); 4.2% with type 1 diabetes, 95.2% with type 2 diabetes, 0.7% with other/unknown diabetes type. In total, 204 AEs were reported in 132 patients (10.0% of the SAS), at a rate [95% confidence interval (CI)] of 16.2 events/100 patient-years of exposure (PYE) [14.0; 18.4]. By preferred term, 'hypoglycaemia' was the most frequent AE (45 events in 31 patients [2.3%]; rate [95% CI] 3.6 events/100 PYE [2.5; 4.6]). Serious AEs occurred in 4.2% of patients (rate [95% CI] 5.7 events/100 PYE [4.4; 7.0]), and ADRs in 3.1% (rate [95% CI] 4.6 reactions/100 PYE [3.4; 5.8]). Six events of severe hypoglycaemia were reported in five patients (0.4%; rate [95% CI] 0.5 events/100 PYE [0.1; 0.9]). Change from baseline to 1 year was - 0.51% and - 32.1 mg/dL for HbA1c and FPG, respectively (P < 0.0001 for both).

Conclusion: In Japanese patients with diabetes, initiation of IDegAsp in real-world clinical practice was well tolerated, with no new safety signals, and associated with improved glycaemic control after 1 year.

Trial registration: ClinicalTrials.gov identifier, NCT02821052.

Keywords: Diabetes; HbA1c; IDegAsp; Japan; Safety.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Patient disposition. *Patients could select more than one reason for discontinuing the study. CRF case report form, EAS effectiveness analysis set, FPG fasting plasma glucose, HbA1c glycated haemoglobin, m months, n number of patients, SAS safety analysis set
Fig. 2
Fig. 2
a Change from baseline in HbA1c, overall and by diabetes type, 1 year after initiation of IDegAsp; b Mean HbA1c (%) by diabetes type over 1 year of treatment. Effectiveness analysis set. Data are observed means (± SEM in a). Data were included for patients with an available HbA1c measurement at a given time point; missing data were not imputed. HbA1c glycated haemoglobin, n number of patients with an HbA1c measurement at time point, T1D type 1 diabetes, T2D type 2 diabetes, SEM standard error of the mean

References

    1. International Diabetes Federation. IDF diabetes atlas. 9th edn. 2019. . Accessed 15 Mar 2021.
    1. Kaku K. Pathophysiology of type 2 diabetes and its treatment policy. JAMA. 2010;52:41–46.
    1. Chan JC, Malik V, Jia W, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009;301(20):2129–2140. doi: 10.1001/jama.2009.726.
    1. Russell-Jones D, Pouwer F, Khunti K. Identification of barriers to insulin therapy and approaches to overcoming them. Diabetes Obes Metab. 2018;20(3):488–496. doi: 10.1111/dom.13132.
    1. Yoshioka N, Ishii H, Tajima N, Iwamoto Y. Differences in physician and patient perceptions about insulin therapy for management of type 2 diabetes: the DAWN Japan study. Curr Med Res Opin. 2014;30(2):177–183. doi: 10.1185/03007995.2013.855187.
    1. Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019;157:107843. doi: 10.1016/j.diabres.2019.107843.
    1. Haahr H, Fita EG, Heise T. A review of insulin degludec/insulin aspart: pharmacokinetic and pharmacodynamic properties and their implications in clinical use. Clin Pharmacokinet. 2017;56(4):339–354. doi: 10.1007/s40262-016-0455-7.
    1. Kumar A, Franek E, Wise J, Niemeyer M, Mersebach H, Simo R. Efficacy and safety of once-daily insulin degludec/insulin aspart versus insulin glargine (U100) for 52 weeks in insulin-naive patients with type 2 diabetes: a randomized controlled trial. PLoS ONE. 2016;11(10):e0163350. doi: 10.1371/journal.pone.0163350.
    1. Kumar S, Jang HC, Demirag NG, Skjoth TV, Endahl L, Bode B. Efficacy and safety of once-daily insulin degludec/insulin aspart compared with once-daily insulin glargine in participants with type 2 diabetes: a randomized, treat-to-target study. Diabet Med. 2017;34(2):180–188. doi: 10.1111/dme.13125.
    1. Hirsch IB, Bode B, Courreges JP, 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. doi: 10.2337/dc11-2503.
    1. Fulcher GR, Christiansen JS, Bantwal G, 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. 2014;37(8):2084–2090. doi: 10.2337/dc13-2908.
    1. Rodbard HW, Cariou B, Pieber TR, Endahl LA, Zacho J, Cooper JG. 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 Obes Metab. 2016;18(3):274–280. doi: 10.1111/dom.12609.
    1. Novo Nordisk. Ryzodeg summary of product characteristics®. 2013. . Accessed 19 Feb 2021.
    1. Novo Nordisk. Ryzodeg® Prescribing information. 2015. . Accessed 19 Feb 2021.
    1. Onishi Y, Ono Y, Rabol 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. doi: 10.1111/dom.12097.
    1. Kaneko S, Chow F, Choi DS, et al. 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 Res Clin Pract. 2015;107(1):139–147. doi: 10.1016/j.diabres.2014.09.026.
    1. Taneda S, Hyllested-Winge J, Gall MA, Kaneko S, Hirao K. Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: subgroup analysis of a Pan-Asian, treat-to-target phase 3 trial. J Diabetes. 2017;9(3):243–247. doi: 10.1111/1753-0407.12407.
    1. Haahr H, Sasaki T, Bardtrum L, Ikushima I. Insulin degludec/insulin aspart in Japanese patients with type 1 diabetes mellitus: distinct prandial and basal glucose-lowering effects. J Diabetes Investig. 2016;7(4):574–580. doi: 10.1111/jdi.12461.
    1. Evaluation and Licensing Division PaFSB. Ryzodeg, report on the deliberation results. 2012.
    1. Pharmaceuticals and Medical Devices Agency. Ryzodeg® combination Injection FlexTouch®. 2020. . Accessed 19 Feb 2021.
    1. Haneda M, Noda M, Origasa H, et al. Japanese clinical practice guideline for diabetes 2016. Diabetol Int. 2018;9(1):1–45. doi: 10.1007/s13340-018-0345-3.
    1. Kaneko S, da Rocha Fernandes JD, Yamamoto Y, Langer J, Faurby M. A Japanese study assessing glycemic control with use of IDegAsp co-formulation in patients with type 2 diabetes in clinical practice: the JAGUAR study. Adv Ther. 2021;38(3):1638–1649. doi: 10.1007/s12325-021-01623-y.
    1. Novo Nordisk A/S. RESILIENT: a research study, looking at how Ryzodeg® works in people with type 2 diabetes in local clinical practice in Japan (RESILIENT). 2019. . Accessed Mar 2021.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit