Intralymphatic GAD-alum (Diamyd®) improves glycaemic control in Type 1 diabetes with HLA DR3-DQ2Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, Spain.
Institution of Clinical Science, Dept of Pediatrics, Umeå university, Norrland University Hospital, Umeå, Sweden.
Department of Pediatric Endocrinology, Cruces University Hospital, Bilbao, Ciberdem, Spain.
Department of Endocrinology, Virgen Macarena Hospital, Sevilla, Spain; Department of Endocrinology and Nutrition, Virgen Macarena University Hospital, Sevilla, Spain.
Diabetes Unit. Department of Endocrinology and Nutrition. Ibima. Ciberdem. General University Hospital, Malaga, Spain.
Department of Pediatrics, NU Hospital Group, Uddevalla, Sweden.
Department of Endocrinology and Nutrition, Vall d'Hebron Hospital, Barcelona, Ciberdem, Spain.
Department of Endocrinology, Pediatric Service, Vall d'Hebron Hospital, Barcelona, Ciberer Spain.
Pediatric Endocrinology Service, Virgen del Rocío University Hospital, Sevilla, Spain.
Department of Pediatric Endocrinology, Miguel Servet University Hospital, Zaragoza, Spain.
Diabeter, National Treatment and Research Center for Children, Adolescents and Young Adults with type 1 diabetes, and Department of Pediatric Endocrinology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Department of Pediatrics, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic; Motol University Hospital, Prague, Czech Republic.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences, Linköping University, Linköping, Sweden.
Diamyd Medical AB, Stockholm, Sweden.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children´s Hospital, Linköping University, Linköping, Sweden.
Division of Pediatrics, Department of Biomedical and Clinical Sciences, Faculty of Medicine and Health Sciences and Crown Princess Victoria Children´s Hospital, Linköping University, Linköping, Sweden.
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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
2022-06-152022-06-152024-01-02Bibliographically approved