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GAD‐treatment of children and adolescents with recent‐onset type 1 diabetes preserves residual insulin secretion after 30 months
Author(s) -
Ludvigsson Johnny,
Chéramy Mikael,
Axelsson Stina,
Pihl Mikael,
Åkerman Linda,
Casas Rosaura
Publication year - 2014
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2503
Subject(s) - medicine , type 1 diabetes , placebo , adverse effect , alum , diabetes mellitus , gastroenterology , clinical trial , insulin , glutamate decarboxylase , subcutaneous injection , type 2 diabetes , pediatrics , endocrinology , biochemistry , chemistry , materials science , alternative medicine , enzyme , pathology , metallurgy
Background This study aimed to analyse data from two different studies (phase II and phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD 65 (GAD‐alum) at 30 months after administration to children and adolescents with type 1 diabetes. Methods The phase II trial was a double‐blind, randomised placebo‐controlled study, including 70 children and adolescents who were followed for 30 months. Participants received a subcutaneous injection of either 20 µg of GAD‐alum or placebo at baseline and 1 month later. During a subsequent larger European phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD‐alum and/or placebo at baseline, 1, 3 and 9 months. The phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow‐up, and 45 patients completed the trial at 30 months. Both studies included GAD 65 auto‐antibodies‐positive patients with fasting C‐peptide ≥0.10 nmol/l. We have now combined the results of these two trials. Results There were no treatment related adverse events. In patients treated with 2 GAD‐alum doses, stimulated C‐peptide area under the curve had decreased significantly less (9 m: p < 0.037; 15 m: p < 0.032; 21 m: p < 0.003 and 30 m: p < 0.004), and a larger proportion of these patients were also able to achieve a peak stimulated C‐peptide >0.2 nmol/L ( p < 0.05), as compared with placebo. Conclusion Treatment with two doses of GAD‐alum in children and adolescents with recent‐onset type 1 diabetes shows no adverse events and preserves residual insulin secretion. Copyright © 2013 John Wiley & Sons, Ltd.