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Safety and glycemic control with insulin degludec use in clinical practice: results from a 3-year Japanese post-marketing surveillance study

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Abstract

Introduction

Insulin degludec (degludec) is a basal insulin with a long duration of action. This post-marketing surveillance study monitored safety and glycemic control during use of degludec for 3 years in normal clinical practice in Japan.

Materials and methods

This multicenter, open-label, observational study included patients with diabetes receiving degludec in Japan between 2013 and 2019. The primary outcome was incidence of adverse events occurring over 3 years of treatment. The pre-specified, secondary outcomes were severe hypoglycemic episodes and changes in HbA1c and fasting plasma glucose levels.

Results

Of 4167 patients enrolled, 4022 were included in the safety assessments and 3918 in the assessments of glycemic control. Mean age was 58.9 years; 74.1% of patients had type 2 diabetes, and mean HbA1c at baseline was 8.7%. Adverse events and serious adverse events were observed in 19.1% and 8.9% of patients, respectively. Cardiac disorders and neoplasms were reported in 2.0% and 1.8% of patients, respectively, with the majority of these incidents reported as serious adverse events. Adverse drug reactions were seen in 8.0% of patients, mainly hypoglycemia. Hypoglycemic events were observed in 5.6% of patients, and severe hypoglycemic events in 1.7%. No serious allergic or injection-site reactions were seen. Respective changes (from baseline to 3 years’ observation) in HbA1c and fasting plasma glucose levels were − 0.55% and − 36.3 mg/dL, and 19.6% of patients reached HbA1c < 7.0%.

Conclusions

Using degludec for 3 years in normal clinical practice had a good safety and tolerability profile. Improvements in glycemic control were also seen.

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Data availability

The data analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors would like to thank all the study investigators and coordinators. Medical writing and editorial support for the development of this manuscript, under the direction of the authors, were provided by Patrick Hoggard, PhD, and Helen Marshall, BA, of Ashfield MedComms, an Inizio company, and funded by Novo Nordisk A/S. Novo Nordisk A/S participated in the study design, site selection, study coordination, data management, data analysis, and study report preparation.

Funding

Novo Nordisk A/S funded this study.

Author information

Authors and Affiliations

  1. Department of Clinical Nutrition, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Takashi Murata

  2. Diabetes Center, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

    Takashi Murata

  3. Novo Nordisk A/S, Søborg, Denmark

    Lise Lotte N. Husemoen

  4. Novo Nordisk Pharma Ltd, Tokyo, Japan

    Satoko Nemoto

  5. Diabetes Therapeutics and Research Center, Institute of Advanced Medical Sciences, Tokushima University, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan

    Munehide Matsuhisa

Authors
  1. Takashi Murata
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  2. Lise Lotte N. Husemoen
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  3. Satoko Nemoto
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  4. Munehide Matsuhisa
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Contributions

TM, LLNH, SN, and MM all fulfil the International Committee of Medical Journal Editors (ICMJE) criteria for authorship. The study was conceptualized, designed, and conducted by employees of Novo Nordisk not in the author list. Authors LLNH and SN were involved in the analysis of the data. TM, LLNH, SN, and MM were involved in data interpretation and the development and critical review of each draft, and all approve the final version to be published.

Corresponding author

Correspondence to Munehide Matsuhisa.

Ethics declarations

Conflict of interest

Takashi Murata has received honoraria from Eli Lilly Japan, Sanofi, Kowa Pharmaceutical, Novo Nordisk, Kyowa Kirin, and Takeda Pharmaceutical; and grants from Sanofi and Kowa Pharmaceutical. Lise Lotte N. Husemoen and Satoko Nemoto are employed by Novo Nordisk. Munehide Matsuhisa has received honoraria from Sanofi, Takeda Pharmaceutical, Eli Lilly Japan, Mitsubishi Tanabe Pharma Corporation, Astellas Pharma, Novo Nordisk, Orizuru Therapeutics, Sumitomo Pharma, Abbott Japan, and MSD; research funding from Sysmex, Nissui, and Tokushima Data Service; and subsidies or donations from Astellas Pharma, Nippon Boehringer Ingelheim, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Novartis, Sanofi, Novo Nordisk, Takeda Pharmaceutical, MSD, and Ono Pharmaceutical.

Ethical approval

The study was conducted according to requirements of the revised Declaration of Helsinki, the Guidelines for Good Pharmacoepidemiology Practices, the Japanese Ministry of Health, Labour and Welfare Notification No. 171, “Ordinance Concerning the Standards for Conducting Post-Marketing Surveys and Studies on Drugs”, and the Japanese Ministry of Health, Labour and Welfare Notification No. 135, “Ordinance Concerning the Standards for Post-Marketing Safety Management of Drugs, Medical Devices, Cosmetics and Medical Devices” (GVP; issued 22 September 2004). The protocol and any amendments were approved at each investigator site, as required locally. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and/or with the Helsinki Declaration of 1964 and later versions.

Informed consent

All participants or legally acceptable representatives (for children) provided written informed consent. Prior to study-related activities and commencement of degludec, the physician had to provide written and oral study information to the patient/representative to be read and understood.

Approval date of registry and the registration no. of the study/trial

This study was pre-registered to ensure transparency and minimize selective reporting bias. The first submitted date was 07 November 2013 and the first posted date was 14 November 2013. The ClinicalTrials.gov registration number is NCT01984372.

Animal studies

N/A.

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Murata, T., Husemoen, L.L.N., Nemoto, S. et al. Safety and glycemic control with insulin degludec use in clinical practice: results from a 3-year Japanese post-marketing surveillance study. Diabetol Int 15, 76–85 (2024). https://doi.org/10.1007/s13340-023-00657-7

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  • DOI: https://doi.org/10.1007/s13340-023-00657-7

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