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

Diabetes Obes Metab. 2015 Sep;17(9):859-67. doi: 10.1111/dom.12485. Epub 2015 Jun 16.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Female
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Glargine / administration & dosage*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Insulin Glargine