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 300 U/ml (Gla-300) with that of glargine 100 U/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 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6 mmol/l (80-100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. 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/m(2) 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 (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [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.

Trial registration: ClinicalTrials.gov NCT01676220.

Keywords: basal insulin analogues; basal insulin initiation; type 2 diabetes.

Figure 1

Clinical measures (mean ± standard error) during treatment by visit (modified intention-to-treat population): (A) glycated haemoglobin (HbA1c). (B) Laboratory-measured fasting plasma glucose (FPG). (C) Pre-breakfast self-monitored plasma glucose (SMPG). (D) Daily basal insulin dose. For data values, please refer to Table1 (HbA1c, laboratory-measured FPG and pre-breakfast SMPG) and Results (insulin dose). Gla-100, glargine 100 U/ml; Gla-300, glargine 300 U/ml.

Figure 2

Hypoglycaemic events during the night (00:00–00:59 hours) or at any time of day (24 h) with glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) during 6 months of treatment (safety population): (A) Relative risk of at least one hypoglycaemic event per participant. (B) Ratio of annualized event rates. CI, confidence interval.

Figure 3

Confirmed (≤3.9 mmol/l) or severe hypoglycaemia during 6 months of treatment by time of the day (safety population): (A) Percentage of participants who experienced at least one event and (B) associated between-treatment differences. (C) Annualized event rates (events per participant-year) and (D) associated between-treatment differences. Gla-300, glargine 300 U/ml; Gla-100, glargine 100 U/ml.