title: Efficacy and safety of once-daily insulin degludec dosed flexibly at convenient times vs fixed dosing at the same time each day in a Japanese cohort with type 2 diabetes: A randomized, 26-week, treat-to-target trial.
abstract: OBJECTIVE
  This trial assessed the efficacy and safety of the possibility of varying the daily injection time of once-daily, long-acting basal insulin degludec (IDeg) in Japanese patients with type 2 diabetes inadequately controlled with insulin glargine.
  
  
  METHODS
  This was a 26-week, multicenter, open-label, randomized, treat-to-target trial, with a 2 × 2 factorial design comparing IDeg flexible (allowing dosing ±8 h from an agreed dosing time) with IDeg fixed dosing (at the same time each day). It was carried out in 458 adult patients who were inadequately controlled on insulin glargine with or without oral antidiabetic drugs.
  
  
  RESULTS
  The majority of doses were taken within 2 h of the agreed dosing time, showing a high level of adherence among Japanese patients. After 26 weeks, IDeg flexible was non-inferior to IDeg fixed with respect to change in glycated hemoglobin from baseline, estimated treatment difference 0.08% points (95% confidence interval -0.05; 0.22). Fasting plasma glucose decreased to a similar level with IDeg flexible and IDeg fixed, estimated treatment difference -0.18 mmol/L (95% confidence interval -0.48; 0.12). The rates of confirmed and nocturnal confirmed hypoglycemia were numerically, but not significantly, higher with IDeg flexible vs IDeg fixed dosing. The rates of adverse events with IDeg flexible and IDeg fixed dosing were similar.
  
  
  CONCLUSIONS
  These results showed the efficacy and safety of allowing patients to vary the time they dosed IDeg, when necessary, in Japanese patients with type 2 diabetes. Dosing of IDeg at a time convenient to the patient was non-inferior, with respect to glycated hemoglobin, to dosing at the same time each day.
authors.affiliation: Department of Metabolic Diseases, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: Iryo Houjin Shadan Jinnouchikai, Jinnouchi Hospital, Kumamoto, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Jinnouchi
authors.affiliation: Department of Internal Medicine, Kawasaki Medical School, Okayama, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kaku
authors.affiliation: Medical & Science, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Malene L
authors.initials: ML
authors.lastname: Hersløv
authors.affiliation: Medical & Scientific Affairs, Novo Nordisk Pharma Ltd, Tokyo, Japan.
authors.forename: Jacob
authors.initials: J
authors.lastname: Hyllested-Winge
authors.affiliation: Iryo Houjin Shadan Kowakai Heiwadai Hospital, Miyazaki, Japan.
authors.forename: Shuji
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use*; D007564:Japan; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec
keywords: Basal insulin; Clinical trial; Type 2 diabetes mellitus