title: New Insulin Glargine 300 Units/mL Versus Glargine 100 Units/mL in People With Type 1 Diabetes: A Randomized, Phase 3a, Open-Label Clinical Trial (EDITION 4).
abstract: OBJECTIVE
  Insulin therapy in type 1 diabetes still provides suboptimal outcomes. Insulin glargine 300 units/mL (Gla-300), with a flatter pharmacodynamic profile compared with insulin glargine 100 units/mL (Gla-100), is an approach to this problem.
  
  
  METHODS
  People with type 1 diabetes, using a mealtime and basal insulin regimen, were randomized open-label to Gla-300 or Gla-100 and to morning or evening injection, continuing the mealtime analog, and followed for 6 months.
  
  
  RESULTS
  Participants (n = 549) were a mean age of 47 years and had a mean duration of diabetes of 21 years and BMI of 27.6 kg/m(2). The change in HbA1c (primary end point; baseline 8.1%) was equivalent in the two treatment groups (difference, 0.04% [95% CI -0.10 to 0.19]) (0.4 mmol/mol [-1.1 to 2.1]), and Gla-300 was thus noninferior. Similar results with wider 95% CIs were found for morning and evening injection times and for prebreakfast self-measured plasma glucose (SMPG) overall. Results were also similar for Gla-300 when morning and evening injection time was compared, including overlapping 8-point SMPG profiles. Hypoglycemia did not differ, except for the first 8 weeks of the study, when nocturnal confirmed or severe hypoglycemia was lower with Gla-300 (rate ratio 0.69 [95% CI 0.53-0.91]). Hypoglycemia with Gla-300 did not differ by time of injection. The basal insulin dose was somewhat higher at 6 months for Gla-300. The adverse event profile did not differ and was independent of the Gla-300 time of injection. Weight gain was lower with Gla-300.
  
  
  CONCLUSIONS
  In long-duration type 1 diabetes, Gla-300 provides similar glucose control to Gla-100, with a lower risk of hypoglycemia after transfer from other insulins, independent of time of injection, and less weight gain.
authors.affiliation: Newcastle University, Newcastle upon Tyne, U.K. philip.home@newcastle.ac.uk.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Home
authors.affiliation: International Diabetes Center at Park Nicollet, Minneapolis, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
authors.affiliation: Department of Medicine, Perugia University Medical School, Perugia, Italy.
authors.forename: Geremia B
authors.initials: GB
authors.lastname: Bolli
authors.affiliation: Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Ziemen
authors.affiliation: Sanofi, Morrisville, PA.
authors.forename: Maria
authors.initials: M
authors.lastname: Rojeski
authors.affiliation: Sanofi, Paris, France.
authors.forename: Melanie
authors.initials: M
authors.lastname: Espinasse
authors.affiliation: Oregon Health & Science University, Portland, OR.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Riddle
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine