{ "abstract": "Aims/hypothesis: In the PROTECT randomised trial, teplizumab demonstrated significantly greater beta cell function preservation vs placebo in the intent-to-treat (ITT) population. Analyses of the pre-specified per-protocol (PP) population and PP subgroups are presented to further evaluate the efficacy of teplizumab.\n\nMethods: Participants aged 8–17 years with stage 3 type 1 diabetes with a peak stimulated C-peptide level ≥0.2 nmol/l (ITT population: N=328) were randomised 2:1 to receive two 12-day courses of teplizumab or placebo intravenously. Participants with <80% treatment adherence, who took prohibited medication, received incorrect study treatment or were pregnant were excluded from the PP population. Subgroup analyses were based on the presence of HLA-DR3 or HLA-DR4 and the type of baseline type 1 diabetes autoantibodies.\n\nResults: The PP population comprised 275 participants (teplizumab, n=180; placebo, n=95). At week 78, the primary endpoint of the least squares (LS) mean difference in change of stimulated C-peptide concentration from baseline between teplizumab and placebo was 0.14 nmol/l (95% CI 0.10, 0.18; p<0.001). At week 78, teplizumab treatment significantly reduced the exogenous insulin dose (LS mean difference –0.17 U kg−1 day−1; 95% CI –0.26, –0.08; p<0.001) and increased the time in range (TIR) (LS mean difference 6.17%; 95% CI 0.13, 12.2; p<0.05) vs placebo. In subgroup analyses, treatment with teplizumab resulted in higher C-peptide levels compared with placebo, regardless of HLA-DR3/HLA-DR4 presence or baseline type 1 diabetes autoantibodies.\n\nConclusions/interpretation: Teplizumab treatment per protocol led to greater beta cell function preservation, greater TIR and lower exogenous insulin use compared with placebo. Beta cell function preservation was maintained irrespective of HLA subtype or the presence of type 1 diabetes autoantibodies.\n\nTrial registration: ClinicalTrials.gov NCT03875729\n\nFunding: The study was funded by Provention Bio, a Sanofi company\n\nGraphical Abstract:\n\nSupplementary Information: The online version of this article (https://doi.org/10.1007/s00125-026-06849-5) contains peer-reviewed but unedited supplementary material.", "abstract_shown": true, "affiliations": [ "Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut USA", "Department of Endocrinology, Cardiff University School of Medicine, Cardiff, UK", "Université Paris Cité, CNRS, Inserm, Institut Necker Enfants Malades-INEM, Paris, France", "Department of Pediatrics, University of California San Francisco, San Francisco, CA USA", "Department of Pediatrics, Motol University Hospital and 2nd Faculty of Medicine, Prague, Czechia", "Barbara Davis Center for Diabetes/University of Colorado School of Medicine, Aurora, CO USA", "Department of Pediatric Diabetology and Paediatrics, Medical University of Warsaw, Warsaw, Poland", "Sanofi, Morristown, NJ USA", "Sanofi, Industrial Park Höchst, G879, Frankfurt am Main, Germany", "Provention Bio, Morristown, NJ USA" ], "article_type": "research article", "arxiv": null, "author_total": 13, "authors": [ { "affs": [ 0 ], "name": "Kevan C. Herold", "orcid": "0000-0003-1534-6613" }, { "affs": [ 1 ], "name": "Colin M. Dayan", "orcid": "0000-0002-6557-3462" }, { "affs": [ 2 ], "name": "Lucienne Chatenoud", "orcid": "0000-0002-1328-2786" }, { "affs": [ 3 ], "name": "Stephen E. Gitelman", "orcid": "0000-0003-4186-4107" }, { "affs": [ 4 ], "name": "Zdenek Sumnik", "orcid": "0000-0002-6462-6462" }, { "affs": [ 5 ], "name": "Kimber Simmons", "orcid": "0000-0003-0560-5773" }, { "affs": [ 6 ], "name": "Agnieszka Szypowska", "orcid": "0000-0002-3407-3174" }, { "affs": [ 7 ], "name": "Laura A. Knecht", "orcid": "0009-0001-9347-5819" }, { "affs": [ 8 ], "name": "Elisabeth Niemoeller", "orcid": "0009-0004-4900-6259" }, { "affs": [ 9 ], "name": "Mark R. Rigby", "orcid": "0000-0002-5490-5951" }, { "affs": [ 9 ], "name": "Wei Tian" }, { "affs": [ 7 ], "name": "Robert Hill" }, { "affs": [ 9 ], "name": "Eleanor L. Ramos", "orcid": "0009-0006-7163-5726" } ], "bibtex": "https://research.draconitic.com/paper/e23yqa3s84n3m.bib", "cited_by": 0, "doi": "10.1007/s00125-026-06849-5", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13714163/", "id": "e23yqa3s84n3m", "issns": [ "0012-186X", "1432-0428" ], "landing_url": "https://doi.org/10.1007/s00125-026-06849-5", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Article" ], [ "openalex", "1311|Diabetes and associated disorders" ] ], "openalex": "W7212189602", "pdf_url": "https://link.springer.com/content/pdf/10.1007/s00125-026-06849-5.pdf", "pmcid": "PMC13714163", "pmid": "42720752", "published": "2026-09-10", "publisher": null, "ris": "https://research.draconitic.com/paper/e23yqa3s84n3m.ris", "sources": [ { "first_seen": "2026-11-01T12:21:43Z", "native_id": "PMC13714163", "source": "pmc", "url": "https://doi.org/10.1007/s00125-026-06849-5" } ], "subjects": [ { "field": "biology", "origin": "openalex:1311|Diabetes and associated disorders", "subfield": "genetics-genomics" } ], "title": "Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial", "title_text": "Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial", "type": "peer-reviewed", "updated_at": "2026-11-01T12:21:43Z", "url": "https://research.draconitic.com/paper/e23yqa3s84n3m", "venue": "Diabetologia", "versions": [] }