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

AimTo 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.MethodsThe 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.ResultsGla‐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.ConclusionsIn 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.

New Drug in the Evolution of Long-Acting Insulins

“…Пациенты были рандомизированы в зависимости от вида базально-го инсулина: Gla-300 или Gla-100, доза которого титрова-лась до достижения целевого уровня глюкозы в плазме натощак (ГПН) 4,4-7,2 ммоль/л [9]. Через 6 мес.…”

rDNA insulin glargine U300 – a critical appraisal

“…The clinical efficacy and safety of Gla-300 compared with that of Gla-100 were evaluated in 3,500 people with diabetes in a global (North America, Europe, South Africa, and Japan) series of six pivotal Phase III studies known as the EDITION series, supported by the drug sponsor 24,30,37–40. These were multicenter, randomized, open-label, parallel-group trials with similar study design and outcomes.…”

“…EDITION JP 140 and JP 224 were conducted in Japanese patients with T1DM and T2DM, respectively (Table 1). …”

“…Subjects in the EDITION 1, 2, and JP 2 studies were already receiving basal insulin, either with mealtime insulin (EDITION 1)30 or oral antidiabetes drugs (OADs; EDITION 2 and JP 2);24,37 EDITION 3 was conducted in insulin-naive patients uncontrolled on OADs 38. EDITION 4 and EDITION JP 1 were conducted in subjects with T1DM on mealtime insulin plus either Gla-300 or Gla-100 once daily39,40 (Table 1). …”

“…All the individual EDITION trials were head-to-head studies of Gla-300 vs Gla-100 of 6-month treatment duration, with a preplanned 6-month safety extension phase 24,30,37,38,40. Extension studies to 12 months have been completed and published for EDITION 1 and EDITION 2,41,42 and these data are available as abstracts in two other studies conducted in a Japanese population43,44 (Tables 2 and 3).…”