Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2
Language English Country United States Media print
Document type Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
PubMed
35665810
PubMed Central
PMC9721339
DOI
10.1210/clinem/dgac343
PII: 6602344
Knihovny.cz E-resources
- Keywords
- C-peptide, Diamyd, GAD-alum, GAD65, HLA DR3-DQ2, HbA1c, antigen-specific immune therapy, continuous glucose monitoring, type 1 diabetes,
- MeSH
- C-Peptide MeSH
- Diabetes Mellitus, Type 1 * MeSH
- Child MeSH
- Glutamate Decarboxylase MeSH
- HLA-DR3 Antigen MeSH
- Alum Compounds MeSH
- Blood Glucose MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Glycemic Control MeSH
- Blood Glucose Self-Monitoring MeSH
- Vitamin D therapeutic use MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- aluminum sulfate MeSH Browser
- C-Peptide MeSH
- Glutamate Decarboxylase MeSH
- HLA-DR3 Antigen MeSH
- Alum Compounds MeSH
- Blood Glucose MeSH
- Vitamin D MeSH
AIMS: Residual beta cell function in type 1 diabetes (T1D) is associated with lower risk of complications. Autoantigen therapy with GAD-alum (Diamyd) given in 3 intralymphatic injections with oral vitamin D has shown promising results in persons with T1D carrying the human leukocyte antigen (HLA) DR3-DQ2 haplotype in the phase 2b trial DIAGNODE-2. We aimed to explore the efficacy of intralymphatic GAD-alum on blood glucose recorded by continuous glucose monitoring (CGM). METHODS: DIAGNODE-2 (NCT03345004) was a multicenter, randomized, placebo-controlled, double-blind trial of 109 recent-onset T1D patients aged 12 to 24 years with GAD65 antibodies and fasting C-peptide > 0.12 nmol/L, which randomized patients to 3 intralymphatic injections of 4 μg GAD-alum and oral vitamin D, or placebo. We report results for exploratory endpoints assessed by 14-day CGM at months 0, 6, and 15. Treatment arms were compared by mixed-effects models for repeated measures adjusting for baseline values. RESULTS: We included 98 patients with CGM recordings of sufficient quality (DR3-DQ2-positive patients: 27 GAD-alum-treated and 15 placebo-treated). In DR3-DQ2-positive patients, percent of time in range (TIR, 3.9-10 mmol/L) declined less between baseline and month 15 in GAD-alum-treated compared with placebo-treated patients (-5.1% and -16.7%, respectively; P = 0.0075), with reduced time > 13.9 mmol/L (P = 0.0036), and significant benefits on the glucose management indicator (P = 0.0025). No differences were detected for hypoglycemia. GAD-alum compared to placebo lowered the increase in glycemic variability (standard deviation) observed in both groups (P = 0.0219). Change in C-peptide was correlated with the change in TIR. CONCLUSIONS: Intralymphatic GAD-alum improves glycemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.
Department of Endocrinology and Nutrition Hospital Universitario Ramón y Cajal 28034 Madrid Spain
Department of Endocrinology and Nutrition Vall d'Hebron Hospital 08035 Barcelona Ciberdem Spain
Department of Endocrinology Pediatric Service Vall d'Hebron Hospital 08035 Barcelona CibererSpain
Department of Neurobiology Care Sciences and Society Karolinska Institutet 14183 Huddinge Sweden
Department of Pediatric Endocrinology Cruces University Hospital 48902 Bilbao Ciberdem Spain
Department of Pediatric Endocrinology Miguel Servet University Hospital 50009 Zaragoza Spain
Department of Pediatrics NU Hospital Group 45153 Uddevalla Sweden
Diabetes Centre of the Institute of Clinical and Experimental Medicine 14000 Prague Czech Republic
Diamyd Medical AB 11135 Stockholm Sweden
Pediatric Endocrinology Service Virgen del Rocío University Hospital 41013 Sevilla Spain
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ClinicalTrials.gov
NCT03345004