Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes

Abstract

Aims: To conduct a patient-level meta-analysis of the EDITION 1, 2 and 3 studies, which compared the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with insulin glargine 100 U/ml (Gla-100) in people with type 2 diabetes (T2DM) on basal and mealtime insulin, basal insulin and oral antihyperglycaemic drugs, or no prior insulin, respectively.

Methods: The EDITION studies were multicentre, randomized, open-label, parallel-group, phase IIIa studies, with similar designs and endpoints. A patient-level meta-analysis of the studies enabled these endpoints to be examined over 6 months in a large population with T2DM (Gla-300, n = 1247; Gla-100, n = 1249).

Results: No significant study-by-treatment interactions across studies were found, enabling them to be pooled. The mean change in glycated haemoglobin was comparable for Gla-300 and Gla-100 [each -1.02 (standard error 0.03)%; least squares (LS) mean difference 0.00 (95% confidence interval (CI) -0.08 to 0.07)%]. Annualized rates of confirmed (≤3.9 mmol/l) or severe hypoglycaemia were lower with Gla-300 than with Gla-100 during the night (31% difference in rate ratio over 6 months) and at any time (24 h, 14% difference). Consistent reductions were observed in percentage of participants with ≥1 hypoglycaemic event. Severe hypoglycaemia at any time (24 h) was rare (Gla-300: 2.3%; Gla-100: 2.6%). Weight gain was low (<1 kg) in both groups, with less gain with Gla-300 [LS mean difference -0.28 kg (95% CI -0.55 to -0.01); p = 0.039]. Both treatments were well tolerated, with similar rates of adverse events.

Conclusion: Gla-300 provides comparable glycaemic control to Gla-100 in a large population with a broad clinical spectrum of T2DM, with consistently less hypoglycaemia at any time of day and less nocturnal hypoglycaemia.

Keywords: basal insulin; insulin glargine; insulin therapy.

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

Figures

Figure 1

(A) Glycated haemoglobin (HbA1c), (B) Laboratory-measured fasting plasma glucose (FPG), (C) Insulin dose [modified intention-to-treat (mITT) population and (D) body weight (safety population) by visit during the 6-month treatment period for pooled analysis of all three studies. Gla-100, insulin glargine 100 U/ml; Gla-300, insulin glargine 300 U/ml; LS, least squares; BL, baseline; M, month; s.e, standard error; W, week. LOV, last on-treatment value defined as the last measurement made prior to or on the day of the last investigational product intake during the main 6-month on-treatment period.

Figure 2

Cumulative mean number of confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic events (A) at any time of day (24 h) and (B) during the night (00:00–05:59 hours) for pooled analysis of all three studies (safety population). Gla-100, insulin glargine 100 U/ml; Gla-300, insulin glargine 300 U/ml.

Figure 3

Annualized rates and percentage of participants with ≥1 hypoglycaemic event (A) at any time of day (24 h) and (B) during the night (00:00–05:59 hours) for pooled analysis of all three studies (safety population). Gla-100, insulin glargine 100 U/ml; Gla-300, insulin glargine 300 U/ml; CI, confidence interval; BL, baseline; W, week; M, month.

Figure 4

Annualized rates (events per participant-year) of confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia during 6 months of treatment by time of the day for pooled analysis of all three studies (safety population). Gla-100, insulin glargine 100 U/ml; Gla-300, insulin glargine 300 U/ml.