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)

Diabetes Care. 2015 Dec;38(12):2217-25. doi: 10.2337/dc15-0249. Epub 2015 Jun 17.


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.

Research design and 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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Glargine / administration & dosage*
  • Male
  • Middle Aged
  • Weight Gain


  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Glargine