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)

Y Terauchi, M Koyama, X Cheng, Y Takahashi, M C Riddle, G B Bolli, T Hirose, Y Terauchi, M Koyama, X Cheng, Y Takahashi, M C Riddle, G B Bolli, T Hirose

Abstract

Aims: 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.

Keywords: basal insulin; glycaemic control; insulin analogues; phase III study; randomized trial; type 2 diabetes.

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

Figures

Figure 1
Figure 1
Flow of participants through the main 6‐month period of the EDITION JP 2 study: modified intention‐to‐treat (mITT) and safety populations. Gla‐100; insulin glargine 100 U/ml; Gla‐300; insulin glargine 300 U/ml; HbA1c, glycated haemoglobin.
Figure 2
Figure 2
Glycaemic control and insulin dose endpoints across the 6‐month study period [all modified intention‐to‐treat (mITT) population]. (A) glycated haemoglobin (HbA1c). (B) Laboratory‐measured fasting plasma glucose (FPG). (C) Daily basal insulin dose; data are shown as mean ± standard error. BL, baseline; W, week; M, month; Gla‐100; insulin glargine 100 U/ml; Gla‐300; insulin glargine 300 U/ml.
Figure 3
Figure 3
Confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia over the 6‐month study period (safety population). (A) Relative risk of experiencing ≥1 hypoglycaemic event and rate ratio of hypoglycaemic events during the night (00:00–05:59 h) and at any time of day (24 h). (B) Nocturnal (00:00–05:59 h) annualized rates (events per participant‐year). (C) Cumulative mean number of nocturnal (00:00–05:59 h) events per participant. (D) Annualized rates (events per participant‐year) at any time of day (24 h). (E) Cumulative mean number of events at any time of day (24 h) per participant. (F) Number of confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic events per participant‐year by time of the day. CI, confidence interval; Gla‐100; insulin glargine 100 U/ml; Gla‐300; insulin glargine 300 U/ml; *RR, relative risk/rate ratio.

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