One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension - PubMed (original) (raw)

Randomized Controlled Trial

doi: 10.1111/dom.12472. Epub 2015 May 11.

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Randomized Controlled Trial

One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension

M C Riddle et al. Diabetes Obes Metab. 2015 Sep.

Abstract

Aims: To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial.

Methods: EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed.

Results: Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c -0.17 [95% confidence interval (CI) -0.30 to -0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89-0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75-0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent.

Conclusion: During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between treatments.

Keywords: basal insulin; glycaemic control; insulin glargine; meal-time insulin.

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

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Figures

Figure 1

Figure 1

Participant flow diagram for EDITION 1. Upper portion with open boxes shows flow during the main 6-month study; shaded boxes below indicate flow during the extension phase up to 12 months. Gla-100, glargine 100 U/ml; Gla-300, glargine 300 U/ml; mITT, modified intention-to-treat. *During the main 6-month on-treatment period; †Not mutually exclusive with the reason for treatment discontinuation.

Figure 2

Figure 2

Clinical measures (mean ± standard error) during treatment by visit. (A) glycated haemoglobin (HbA1c) in the modified intention-to treat (mITT) population. (B) Laboratory-measured clinic-collected fasting plasma glucose (FPG) in the mITT population. (C) Daily basal insulin and meal-time insulin dose in the mITT population. (D) Weight change from baseline in the safety population. Gla-100, glargine 100 U/ml; Gla-300, glargine 300 U/ml.

Figure 3

Figure 3

Cumulative mean numbers of confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic events per participant during the 12-month study period (safety population). (A) Events occurring at any time of day (24 h). (B) Nocturnal events (00:00–05:59 hours). Gla-100, glargine 100 U/ml; Gla-300, glargine 300 U/ml [Correction added on May 29: In Figure 3A, the values of Gla-100 and Gla-300 were previously incorrect and these have now been amended in this version].

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