New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: A randomized controlled trial (EDITION 3)

Abstract

Aims: To compare the efficacy and safety of new insulin glargine 300U/ml (Gla-300) with that of glargine 100U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. Methods: The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6mmol/l (80-100mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9mmol/l (≤70mg/dl)] or severe hypoglycaemia from week9 to month6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. Results: Randomized participants (n=878) had a mean (standard deviation) age of 57.7 (10.1)years, diabetes duration 9.8 (6.4)years, body mass index 33.0 (6.7)kg/m2 and HbA1c 8.54 (1.06)% [69.8 (11.6)mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17]% or 0.4 (-1.0 to 1.9)mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9mmol/l) or severe hypoglycaemia from week9 to month6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. Conclusions: Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk.