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

Aim: 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.

Keywords: basal insulin; glycaemic control; insulin analogues; phase III study; randomised trial; type 1 diabetes.

© 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Flow of participants through the main 6‐month period of the EDITION JP 1 study [modified intention‐to‐treat (mITT) and safety populations]. Gla‐100, insulin glargine 100 U/ml; Gla‐300, insulin glargine 300 U/ml.

Figure 2

Clinical measures across the 6‐month study period in the modified intention‐to‐treat (mITT) population: (A) glycated haemoglobin (HbA1c), (B) laboratory‐measured fasting plasma glucose (FPG), (C) average pre‐injection self‐monitored plasma glucose (SMPG) profile and (D) daily basal and mealtime insulin dose. Data are shown as mean ± standard error. Gla‐100, insulin glargine 100 U/ml; Gla‐300, insulin glargine 300 U/ml; BL, baseline; W, week; M, month; LOCF, last observation carried forward.

Figure 3

Mean eight‐point self‐monitored plasma glucose (SMPG) profiles at baseline and month 6 (LOCF; modified intention‐to‐treat population). Data are shown as mean ± standard error. Gla‐100, insulin glargine 100 U/ml; Gla‐300, insulin glargine 300 U/ml; LOCF, last observation carried forward.

Figure 4

Occurrence of confirmed or severe hypoglycaemic events during the 6‐month study period (safety population): (A) cumulative mean number of confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe events per participant at any time (24 h) and (B) events per participant‐year; (C) cumulative mean number of nocturnal (00:00–05:59 h) confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe events per participant and (D) events per participant‐year; (E) ratio of event rates and (F) relative risk, during the night (00:00–05:59 h) and at any time (24 h). CI, confidence interval.