Insulin degludec in a simple or stepwise titration algorithm in a Japanese population of patients with type 2 diabetes: a randomized, 26-week, treat-to-target trial

Abstract

Aims: Managing insulin therapy is a challenge for both patients and healthcare providers.The primary aim of this trial was to compare the efficacy and safety of insulin degludec (IDeg) in a fixed versus flexible dosing schedule. The secondary aim and subject of this manuscript was to compare a simple versus a stepwise titration algorithm.

Materials and methods: This was a 26-week, controlled, multicenter, open-label, randomized, treat-to-target phase 3b trial of Japanese patients with type 2 diabetes inadequately treated with insulin glargine and with/without antidiabetic drugs orally. The trial had a 2 × 2 factorial design whereby 458 patients were randomized 1:1:1:1 to one of two titration algorithms and one of two dosing schedules. IDeg dose was adjusted weekly using a clinician-led, treat-to-target approach in order to ensure optimal insulin titration and glycemic control following self-measured blood glucose (SMBG) readings.

Results: Mean insulin dose at the end of the trial was similar in both simple and stepwise titration algorithms. Glycemic control improved in both titration algorithms, with noninferiority in glycated hemoglobin (HbA1c) reduction confirmed when comparing simple and stepwise titration algorithms and no significant differences in fasting plasma glucose or SMBG at 26 weeks. No safety concerns were observed in terms of adverse events, and rates of hypoglycemia were not significantly different between the two algorithms.

Conclusions: This trial demonstrated comparable efficacy with noninferior HbA1c and comparable safety of once-daily IDeg using either a simple or stepwise titration algorithm in Japanese patients with type 2 diabetes inadequately controlled with insulin glargine.

Keywords: Basal insulin; Insulin degludec; Titration algorithm; Type 2 diabetes.

Conflict of interest statement

TK is a member of the National Advisory Board for Novo Nordisk Japan; reports funded research courses from MSD, Nippon Boehringer Ingelheim, Novartis, Takeda and Novo Nordisk; lecture fees from Astellas, AstraZeneca, Eli Lilly, Kissei, Kowa, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim, Novo Nordisk, Ono, Sumitomo Dainippon, and Takeda; manuscript fees from Eli Lilly; scholarship grants and endowments from Daiichi Sankyo, Mitsubishi Tanabe, Sumitomo Dainippon, and Takeda; and funds for clinical research from Daiichi Sankyo, Sanwa Kagaku, and Takeda. HJ has received lecture fees and clinical research grants from AstraZeneca, Astellas Pharma, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Takeda, Novartis Pharmaceuticals, Novo Nordisk and Sanofi. KK has received lecture fees from Astellas, Kissei, Sumitomo Dainippon Pharma, Sanwa Kagaku Kenkyusho Co., Sanofi, Novo Nordisk Pharma, Takeda, Ono Pharmaceutical Co., MSD, Novartis, Boehringer Ingelheim, Mitsubishi Tanabe Pharma, Taisho Toyama Pharmaceutical Co. and Kowa Pharmaceuticals. MLH and JH-W are employees of Novo Nordisk. SN has received honoraria for lectures from Novo Nordisk Pharma Ltd. All authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript and were involved in data interpretation, drafting/critically revising the article, and shared in the final responsibility for the content of the manuscript and the decision to submit it for publication, and take full responsibility for the contents.All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki 1964 and later versions.Informed consent or substitute for it was obtained from all patients for being included in the study.

Figures

Fig. 1

Patient disposition. FAS full analysis set, IDeg insulin degludec, SAS safety analysis set

Fig. 2

Daily dose of insulin degludec according to simple (a) and stepwise (b) titration algorithm: prescribed and actual dose taken. Data are SAS, LOCF. LOCF last observation carried forward, SAS safety analysis set, U units of insulin

Fig. 3

Glycated hemoglobin (HbA1c) over time. Data are FAS; LOCF. CI confidence interval, IDeg insulin degludec, LOCF last observation carried forward, SAS safety analysis set