TitleIntralymphatic GAD-Alum Therapy Preserves C-Peptide in Some Patients With Recent-Onset Type 1 Diabetes
Intralymphatic administration of aluminum-formulated glutamic acid decarboxylase (GAD-alum), combined with vitamin D supplementation, seems to preserve C-peptide in patients with recent-onset type 1 diabetes carrying HLA DR3-DQ2, according to a study published in Diabetes Care.
The phase 2 double-blinded DIAGNODE-2 study included 109 patients aged 12 to 24 years with a diabetes duration of 7 to 193 days, elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L. Patients were randomised to receive either 3 intralymphatic injections (1 month apart) with 4 mcg GAD-alum and oral vitamin D 2,000 IE daily for 120 days, or placebo.
The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months.
The primary end point was not met in the full analysis set (treatment effect ratio = 1.091; P = .5009). However, GAD-alum-treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557; P = .0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17).
Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose-adjusted haemoglobin A1C ≤9; P = .0310). Minor transient injection site reactions were reported.
“The patients in the subgroup with the DR3-DQ2 type of HLA genes did not lose insulin production as quickly as the other patients,” said Johnny Ludvigsson, MD, Linköping University, Linköping, Sweden, and colleagues. “In contrast, we did not see any significant effect in the patients who did not have this HLA type. Treatment with GAD-alum seems to be a promising, simple and safe way to preserve insulin production in around half of patients with type 1 diabetes, the ones who have the right type of HLA. This is why we are looking forward to carrying out larger studies, and we hope these will lead to a drug that can change the progress of type 1 diabetes.”
SOURCE: Linköping University