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.
OBJECTIVE
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.


CONCLUSIONS
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.
Klinikum Schwabing, Städtisches Klinikum München GmbH, Munich, Germany.
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Ritzel
Diabetology Endocrinology Nutrition, DHU FIRE, Bichat Hospital, Assistance Publique Hôpitaux de Paris, Paris, France.|INSERM U1138, Centre de Recherche des Cordeliers, Paris, France.|UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
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Roussel
Department of Medicine, University of Perugia, Perugia, Italy.
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Bolli
EXPERIS IT, Nanterre, France.
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Vinet
Sanofi, Paris, France.
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Brulle-Wohlhueter
Sanofi, Paris, France.
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S
Glezer
Division of Diabetes, Faculty of Medicine and Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland.
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Yki-Järvinen
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D000069036:Insulin Glargine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; C517652:hemoglobin A1c protein, human
basal insulin; insulin glargine; insulin therapy