title: New insulin glargine 300 U/ml versus glargine 100 U/ml in Japanese people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: glucose control and hypoglycaemia in a randomized controlled trial (EDITION JP 2).
abstract: OBJECTIVE
  To compare the efficacy and safety of insulin glargine 300 U/ml (Gla-300) with glargine 100 U/ml (Gla-100) in Japanese people with type 2 diabetes using basal insulin plus oral antihyperglycaemic drug(s) [OAD(s)].
  
  
  METHODS
  The EDITION JP 2 study (NCT01689142) was a 6-month, multicentre, open-label, phase III study. Participants (n = 241, male 61%, mean diabetes duration 14 years, mean weight 67 kg, mean body mass index 25 kg/m(2), mean glycated haemoglobin (HbA1c) 8.02 %, mean basal insulin dose 0.24 U/kg/day) were randomized to Gla-300 or Gla-100, while continuing OAD(s). Basal insulin was titrated to target fasting self-monitored plasma glucose 4.4-5.6 mmol/l. The primary efficacy endpoint was HbA1c change over 6 months. Safety endpoints included hypoglycaemia and weight change.
  
  
  RESULTS
  Gla-300 was non-inferior to Gla-100 for HbA1c reduction [least squares (LS) mean difference 0.10 (95% confidence interval [CI] -0.08, 0.27) %]. The mean HbA1c at month 6 was 7.56 and 7.52 % with Gla-300 and Gla-100, respectively. Nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia risk was 38% lower with Gla-300 versus Gla-100 [relative risk 0.62 (95% CI 0.44, 0.88)]; annualized rates were 55% lower at night [rate ratio 0.45 (95% CI 0.21, 0.96)] and 36% lower at any time [24 h; rate ratio 0.64 (95% CI 0.43, 0.96)]. Severe hypoglycaemia was infrequent. A significant between-treatment difference in weight change favoured Gla-300 [LS mean difference -1.0 (95% CI -1.5, -0.5) kg; p = 0.0003]. Adverse event rates were comparable between groups.
  
  
  CONCLUSIONS
  Japanese people with type 2 diabetes using basal insulin plus OAD(s) experienced less hypoglycaemia with Gla-300 than with Gla-100, while glycaemic control did not differ.
authors.affiliation: Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Terauchi
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: D000284:Administration, Oral; D000368:Aged; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; 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; randomized trial; type 2 diabetes