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Cited by 55Diabetes and associated disordersDiabetes Management and ResearchViral Infections and Immunology Research

Pleconaril and ribavirin in new-onset type 1 diabetes: a phase 2 randomized trial

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Krogvold, Lars, Mynarek, Ida Maria, Ponzi, Erica, Mørk, Freja Barrett, Hessel, Trine Witzner, Roald, Trine, Lindblom, Nina, Westman, Jacob +6 more·2023·Nature Medicine
DOI 10.1038/s41591-023-02576-1PMC PMC10667091
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Abstract

Previous studies showed a low-grade enterovirus infection in the pancreatic islets of patients with newly diagnosed type 1 diabetes (T1D). In the Diabetes Virus Detection (DiViD) Intervention, a phase 2, placebo-controlled, randomized, parallel group, double-blind trial, 96 children and adolescents (aged 6–15 years) with new-onset T1D received antiviral treatment with pleconaril and ribavirin (n = 47) or placebo (n = 49) for 6 months, with the aim of preserving β cell function. The primary endpoint was the mean stimulated C-peptide area under the curve (AUC) 12 months after the initiation of treatment (less than 3 weeks after diagnosis) using a mixed linear model. The model used longitudinal log-transformed serum C-peptide AUCs at baseline, at 3 months, 6 months and 1 year. The primary endpoint was met with the serum C-peptide AUC being higher in the pleconaril and ribavirin treatment group compared to the placebo group at 12 months (average marginal effect = 0.057 in the linear mixed model; 95% confidence interval = 0.004–0.11,P = 0.037). The treatment was well tolerated. The results show that antiviral treatment may preserve residual insulin production in children and adolescent with new-onset T1D. This provides a rationale for further evaluating antiviral strategies in the prevention and treatment of T1D. European Union Drug Regulating Authorities Clinical Trials identifier:2015-003350-41.

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  • Treatment with pleconaril together with ribavirin temporarily preserves β-cell function more effectively than placebo; however, the benefit was not found to be present after 2 years and after 3 years.

    “Treatment with the viral clearing agent pleconaril, together with the broadspectrum antiviral drug ribavirin, temporarily preserves βcell function more effectively than placebo (table 1); 29 however, the benefit was not found to be present after 2 years and after 3 years.30”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [29]

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References 53 · Cited by 55

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Authors
Krogvold, L., Mynarek, I. M., Ponzi, E., Mørk, F. B., Hessel, T. W., Roald, T., Lindblom, N., Westman, J., Barker, P., Hyöty, H., Ludvigsson, J., Hanssen, K. F., Johannesen, J., & Dahl-Jørgensen, K.
Affiliations
  • Oslo University Hospital (NO)
  • University of Copenhagen (DK)
  • Apodemus (Sweden) (SE)
  • National Institute for Health and Care Research (GB)
  • Tampere University (FI)
  • Linköping University (SE)
  • University of Oslo (NO)
  • Herlev Hospital (DK)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2023-10-04
Volume
29
Issue
11
Pages
2902-2908
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-023-02576-1
PMC
PMC10667091
OpenAlex
W4387301346
Cited by
55
References
53
Citations by year
2026: 8 · 2025: 17 · 2024: 28 · 2023: 2
FWCI
9.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Medicine (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
  • DiVA (Linkoping University) (submittedVersion, other-oa)
  • Tampere University Institutional Repository (Tampere University) (submittedVersion, cc-by)
  • NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
Funders
  • Leona M. and Harry B. Helmsley Charitable Trust (115797)
  • Helsingin Yliopisto
  • European Federation of Pharmaceutical Industries and Associations (IMI2-JU, 948268, 115797)
  • Steno Diabetes Center Copenhagen (SDCC 3.D Type1 Biology)
  • European Commission (HORIZON2020, COVID-19, 115797, 948268)
  • Cardiff University
  • Universitetet i Oslo
  • Göteborgs Universitet
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
Keywords
type 1 diabetes, pleconaril, ribavirin, antiviral therapy, enterovirus infection, pancreatic islets, beta-cell function, C-peptide, children and adolescents, new-onset diabetes
MeSH terms
Adolescent, Antiviral Agents, C-Peptide, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Humans, Oxadiazoles, Oxazoles, Ribavirin

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