Glycaemic control and hypoglycaemia during 12 months of randomized treatment with insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 1 diabetes (EDITION 4)

Philip D Home, Richard M Bergenstal, Geremia B Bolli, Monika Ziemen, Maria Rojeski, Melanie Espinasse, Matthew C Riddle, Philip D Home, Richard M Bergenstal, Geremia B Bolli, Monika Ziemen, Maria Rojeski, Melanie Espinasse, Matthew C Riddle

Abstract

Aims: Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM).

Methods: EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM who completed the 6 months continued randomized Gla-300 or Gla-100 once daily, morning or evening, for a further 6 months.

Results: Among 549 participants randomized, 444 completed the 12-month study period (Gla-300, 80%; Gla-100, 82%). Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups (difference, 0.02 [95% CI, -0.13 to 0.17]) %-units [0.2 (-1.5 to 1.9) mmol/mol]), to a mean of 7.86 %-units (62.4 mmol/mol) in both groups. For morning vs evening injection, there was no difference in HbA1c change over 12 months for Gla-100, but a significantly larger decrease in HbA1c was observed in the Gla-300 morning group than in the Gla-300 evening group (difference, -0.25 [-0.47 to -0.04] %-units [-2.7 (-5.2 to -0.4) mmol/mol]). Mean glucose from the 8-point SMPG profiles decreased from baseline, and was similar between the 2 treatment groups. Basal insulin dose was 20% higher with Gla-300 than with Gla-100, while hypoglycaemia event rates, analysed at night, over 24 hours, or according to different glycaemic thresholds, did not differ between treatment groups, regardless of injection time. Adverse event profiles did not differ between groups.

Conclusions: In T1DM, Gla-300 provides glucose control comparable to that of Gla-100, and can be given at any time of day.

Trial registration: ClinicalTrials.gov NCT01683266.

Keywords: analogues; basal insulin; clinical trial; glycaemic control; hypoglycaemia; insulin; type 1 diabetes.

Conflict of interest statement

P. D. H. or his affiliated institutions receive funding from AntriaBio, AstraZeneca, Biocon, GlaxoSmithKline, Hanmi, Janssen, Merck (MSD), Novo Nordisk, Roche Diagnostics and Sanofi. R. M. B. received research support from, served as a consultant for, or served on a scientific advisory board for Abbott Diabetes Care, Amylin, Bayer, Becton Dickinson, Boehringer Ingelheim, Bristol‐Myers Squibb‐AstraZeneca Alliance, Calibra, Dexcom, Eli Lilly, Halozyme, Hygieia, Johnson & Johnson, Medtronic, Merck, Novo Nordisk, Roche, Sanofi and Takeda. R. M. B.’s employer, nonprofit Park Nicollet Institute, contracts for his services and he receives no personal income. R. M. B. has inherited Merck stock. R. M. B. has been a volunteer for the American Diabetes Association and JDRF. G. B. B. received honoraria for advising and lecturing from Eli Lilly, Novartis and Sanofi. M. Z., M. R. and M. E. are employees of Sanofi. M. Z. and M. E. hold stocks/shares in Sanofi. M. C. R. received research grant support from AstraZeneca, Eli Lilly and Sanofi, and honoraria for consulting and/or speaking from AstraZeneca Alliance, Biodel, Elcelyx, Eli Lilly, GlaxoSmithKline, Sanofi, Theracos and Valeritas. M. C. R.’s dualities of interest have been reviewed and managed by Oregon Health and Science University. No other potential conflicts of interest relevant to this article were reported.

© 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1
Figure 1
Time course of daily insulin dose (A), body weight change from baseline (B), glycated haemoglobin (C), glycated haemoglobin by basal insulin injection time (D), laboratory‐measured clinic FPG (E), laboratory‐measured clinic FPG by basal insulin injection time (F), SMPG profiles (G) and SMPG profiles by basal insulin injection time (H) over 12 months of treatment with Gla‐300 or Gla‐100. mITT population, except body weight change (safety population). Baseline body weight = 81.9 and 81.8 kg for Gla‐300 and Gla‐100 groups, respectively. Mean ± SE. BL, baseline; D, day; FPG, laboratory‐measured clinic fasting plasma glucose; LOV, last on‐treatment value; M, month; mITT, modified intention‐to‐treat; SE, standard error; SMPG, self‐monitored plasma glucose; W, week
Figure 2
Figure 2
Cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events per participant during 12 months of treatment with Gla‐300 or Gla‐100: A, events at any time of day (24 hours) and B, nocturnal events. Safety population

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