Glutamic acid decarboxylase immunotherapy for type 1 diabetes.

Curr Opin Endocrinol Diabetes Obes

Crown Princess Victoria Children's Hospital and Division of Pediatrics, Departmentt of Biomedical and Clinical Sciences, Linköping University, Sweden.

Published: August 2022

Purpose Of Review: To describe recent development of an autoantigen (GAD) treatment towards well tolerated and efficacious precision medicine in type 1 diabetes.

Recent Findings: Although subcutaneous GAD-alum treatment failed to reach primary endpoint in a phase III trial, metanalyses showed a 97% probability of efficacy, and clear efficacy in patients carrying Hyman Leucoycte Antigen (HLA) DR3DQ2. Efforts have been made to improve efficacy by trying combination therapies with vitamin D + Ibuprofen resp vitamin D + Etanercept (TNF-α inhibition), without any breakthrough until the administration of GAD-alum was changed from subcutaneous to intralymphatic. With a very small dose of GAD-alum (4 μg) given into an inguinal lymph three times with 1 month interval, the efficacy in patients with HLADR3DQ2 has been impressive, with significantly better beta cell preservation than patients who got placebo in a double-blind randomized trial, and clinical efficacy with more patients in partial remission (IDAA1c < 9) and larger proportion of patients with CGM-measured blood glucose Time In Range (TIR), significantly correlated to the C-peptide values. The treatment has been easy for patients and healthcare without treatment-related risk or adverse events.

Summary: Intralymphatic GAD-alum treatment in type 1 diabetes patients carrying HLA DR3DQ2 seems to be an attractive immune intervention.

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http://dx.doi.org/10.1097/MED.0000000000000748DOI Listing

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