title: New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese adults with type 1 diabetes using basal and mealtime insulin: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 1).
abstract: OBJECTIVE
  To compare efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of insulin glargine 100 U/ml (Gla-100) in Japanese adults with type 1 diabetes.
  
  
  METHODS
  The EDITION JP 1 study (NCT01689129) was a 6-month, multicentre, open-label, phase III study. Participants (n = 243) were randomized to Gla-300 or Gla-100 while continuing mealtime insulin. Basal insulin was titrated with the aim of achieving a fasting self-monitored plasma glucose target of 4.4-7.2 mmol/l. The primary endpoint was change in glycated haemoglobin (HbA1c) over 6 months. Safety measures included hypoglycaemia and change in body weight.
  
  
  RESULTS
  Gla-300 was non-inferior to Gla-100 for the primary endpoint of HbA1c change over the 6-month period {least squares [LS] mean difference 0.13 % [95 % confidence interval (CI) -0.03 to 0.29]}. The annualized rate of confirmed (≤3.9 mmol/l) or severe hypoglycaemic events was 34 % lower with Gla-300 than with Gla-100 at night [rate ratio 0.66 (95 % CI 0.48-0.92)] and 20 % lower at any time of day [24 h; rate ratio 0.80 (95 % CI 0.65-0.98)]; this difference was most pronounced during the first 8 weeks of treatment. Severe hypoglycaemia was infrequent. The basal insulin dose increased in both groups (month 6 dose: Gla-300 0.35 U/kg/day, Gla-100 0.29 U/kg/day). A between-treatment difference in body weight change over 6 months favouring Gla-300 was observed [LS mean difference -0.6 kg (95 % CI -1.1 to -0.0); p = 0.035]. Adverse event rates were comparable between the groups.
  
  
  CONCLUSIONS
  In Japanese adults with type 1 diabetes using basal plus mealtime insulin, less hypoglycaemia was observed with Gla-300 than with Gla-100, particularly during the night, while glycaemic control did not differ.
authors.affiliation: Tokushima University, Tokushima, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Matsuhisa
authors.affiliation: Sanofi, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Koyama
authors.affiliation: Sanofi, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Sanofi, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Oregon Health & Science University, Portland, OR, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Riddle
authors.affiliation: Perugia University Medical School, Perugia, Italy.
authors.forename: G B
authors.initials: GB
authors.lastname: Bolli
authors.affiliation: Toho University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000328:Adult; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D018432:Drug Resistance, Multiple; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000069057:Insulin Detemir / Q000009:adverse effects / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012306:Risk
chemical_list: D003692:Delayed-Action Preparations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069057:Insulin Detemir; D000069036:Insulin Glargine; C517652:hemoglobin A1c protein, human
keywords: basal insulin; glycaemic control; insulin analogues; phase III study; randomised trial; type 1 diabetes