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Intralymphatic GAD-alum (Diamyd®) improves glycaemic control in Type 1 diabetes with HLA DR3-DQ2
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Diamyd Medical AB, Stockholm, Sweden.
Department of Molecular and Clinical Medicine, University of Gothenburg, Gothenburg, Sweden; Sahlgrenska University Hospital, Gothenburg, Sweden; NU-Hospital Group, Uddevalla, Sweden.
Department of Pediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Motol University Hospital, Prague, Czech Republic.
Diabetes Centre of the Institute of Clinical and Experimental Medicine, Prague, Czech Republic.
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2022 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 107, no 9, p. 2644-2651Article in journal (Refereed) Published
Abstract [en]

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 three intralymphatic injections with oral Vitamin D has shown promising results in persons with T1D carrying the HLA DR3-DQ2 haplotype in the phase IIb 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 12-24 years with GAD65 antibodies and fasting C-peptide >0.12 nmol/L, which randomized patients to three 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, % time in range (TIR, 3.9-10 mmol/L) declined less between baseline and Month 15 in GAD-alum-treated compared to 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 hypoglycaemia. GAD-alum compared to placebo lowered the increase in glycaemic 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 glycaemic control in recently diagnosed T1D patients carrying HLA DR3-DQ2.

Place, publisher, year, edition, pages
Oxford University Press, 2022. Vol. 107, no 9, p. 2644-2651
Keywords [en]
C-peptide, Diamyd, GAD-alum, GAD65, HLA DR3-DQ2, HbA1c, Type 1 diabetes, antigen-specific immune therapy, continuous glucose monitoring
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-99531DOI: 10.1210/clinem/dgac343ISI: 000818061200001PubMedID: 35665810Scopus ID: 2-s2.0-85134420398OAI: oai:DiVA.org:oru-99531DiVA, id: diva2:1670023
Funder
DiabetesfondenSwedish Child Diabetes Foundation
Note

Funding agency:

Diamyd Medical AB

Available from: 2022-06-15 Created: 2022-06-15 Last updated: 2024-01-02Bibliographically approved

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Wahlberg, Jeanette

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