{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T00:30:04Z","timestamp":1793406604610,"version":"4.5.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims\/hypothesis<\/jats:title>\n                    <jats:p>Teplizumab is approved in the USA and seven other countries to delay stage 3 type 1 diabetes onset in individuals \u22658 years of age with stage 2 type 1 diabetes. As part of a US Food and Drug Administration post-marketing requirement, this study evaluated the safety, tolerability and pharmacokinetics of teplizumab in children aged &lt;8 years with stage 2 type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The PETITE-T1D trial is a 2 year single-arm, open-label, multicentre study of 23 children &lt;8 years of age with stage 2 type 1 diabetes. Participants received a 14 day teplizumab course. A prespecified interim analysis was performed after 15 participants completed 1 year of follow-up and included all 23 participants. Primary endpoints included treatment-emergent adverse events (TEAEs), TEAEs causing treatment discontinuation, and serious adverse events (SAEs). Other endpoints assessed immunogenicity, pharmacokinetics, pharmacodynamics and time from study treatment to stage 3 type 1 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mean participant age was 4.8 years (range 1.7\u20136.8). Median follow-up duration was 51.9 weeks (range 3.9\u201377.1). All participants experienced one or more TEAE, with most being mild to moderate. No grade 4 or 5 TEAEs were reported. Three participants (13%) had TEAEs leading to teplizumab discontinuation: anaemia, elevated liver enzymes and maculo-papular rash. Two participants (9%) each had two SAEs. Serum teplizumab concentrations peaked at day 14. Two participants progressed to stage 3 type 1 diabetes. The estimated probability of lack of progression to stage 3 was 89.6% (95% CI 64.3%, 97.3%) at the time of interim analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Teplizumab was safe and well tolerated in children &lt;8 years of age with stage 2 type 1 diabetes. Adverse events were consistent with those seen in previous studies, with no new safety risks identified. Two participants progressed to stage 3 type 1 diabetes during the observation period; surveillance is ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT05757713.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-025-06586-1","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T10:06:06Z","timestamp":1762423566000},"page":"330-342","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Safety and pharmacokinetics of teplizumab in children less than 8 years of age with stage 2 type 1 diabetes"],"prefix":"10.1007","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-4107","authenticated-orcid":false,"given":"Stephen E.","family":"Gitelman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0560-5773","authenticated-orcid":false,"given":"Kimber","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9301-3043","authenticated-orcid":false,"given":"Jennifer L.","family":"Sherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0784-7605","authenticated-orcid":false,"given":"Steven B.","family":"Leichter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2385-9278","authenticated-orcid":false,"given":"Teresa","family":"Quattrin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7609-0434","authenticated-orcid":false,"given":"William E.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvana","family":"Sunil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-2425","authenticated-orcid":false,"given":"Steven M.","family":"Willi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Knecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Niemoeller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3389-0735","authenticated-orcid":false,"given":"Idlir","family":"Licaj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Schmider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-6078","authenticated-orcid":false,"given":"Linda A.","family":"DiMeglio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"issue":"5","key":"6586_CR1","doi-asserted-by":"publisher","first-page":"773","DOI":"10.1097\/EDE.0b013e31829ef01a","volume":"24","author":"A Menke","year":"2013","unstructured":"Menke A, Orchard TJ, Imperatore G, Bullard KM, Mayer-Davis E, Cowie CC (2013) The prevalence of type 1 diabetes in the United States. Epidemiology 24(5):773\u2013774. https:\/\/doi.org\/10.1097\/EDE.0b013e31829ef01a","journal-title":"Epidemiology"},{"issue":"2","key":"6586_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2337\/dc22-0945","volume":"46","author":"T Tonnies","year":"2023","unstructured":"Tonnies T, Brinks R, Isom S et al (2023) Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2060: the SEARCH for diabetes in youth study. Diabetes Care 46(2):313\u2013320. https:\/\/doi.org\/10.2337\/dc22-0945","journal-title":"Diabetes Care"},{"issue":"6","key":"6586_CR3","doi-asserted-by":"publisher","first-page":"161","DOI":"10.15585\/mmwr.mm6906a3","volume":"69","author":"J Divers","year":"2020","unstructured":"Divers J, Mayer-Davis EJ, Lawrence JM et al (2020) Trends in incidence of type 1 and type 2 diabetes among youths - selected counties and Indian reservations, United States, 2002\u20132015. MMWR Morb Mortal Wkly Rep 69(6):161\u2013165. https:\/\/doi.org\/10.15585\/mmwr.mm6906a3","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"8","key":"6586_CR4","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.2337\/dci24-0042","volume":"47","author":"M Phillip","year":"2024","unstructured":"Phillip M, Achenbach P, Addala A et al (2024) Consensus guidance for monitoring individuals with islet autoantibody-positive pre-stage 3 type 1 diabetes. Diabetes Care 47(8):1276\u20131298. https:\/\/doi.org\/10.2337\/dci24-0042","journal-title":"Diabetes Care"},{"issue":"17","key":"6586_CR5","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1056\/NEJM199010253231704","volume":"323","author":"WJ Riley","year":"1990","unstructured":"Riley WJ, Maclaren NK, Krischer J et al (1990) A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. N Engl J Med 323(17):1167\u20131172. https:\/\/doi.org\/10.1056\/NEJM199010253231704","journal-title":"N Engl J Med"},{"issue":"43","key":"6586_CR6","doi-asserted-by":"publisher","first-page":"17040","DOI":"10.1073\/pnas.0705894104","volume":"104","author":"JM Wenzlau","year":"2007","unstructured":"Wenzlau JM, Juhl K, Yu L et al (2007) The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes. Proc Natl Acad Sci U S A 104(43):17040\u201317045. https:\/\/doi.org\/10.1073\/pnas.0705894104","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"23","key":"6586_CR7","doi-asserted-by":"publisher","first-page":"2473","DOI":"10.1001\/jama.2013.6285","volume":"309","author":"AG Ziegler","year":"2013","unstructured":"Ziegler AG, Rewers M, Simell O et al (2013) Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 309(23):2473\u20132479. https:\/\/doi.org\/10.1001\/jama.2013.6285","journal-title":"JAMA"},{"issue":"6","key":"6586_CR8","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s11892-022-01465-0","volume":"22","author":"M Monaghan","year":"2022","unstructured":"Monaghan M, Bryant BL, Inverso H, Moore HR, Streisand R (2022) Young children with type 1 diabetes: recent advances in behavioral research. Curr Diab Rep 22(6):247\u2013256. https:\/\/doi.org\/10.1007\/s11892-022-01465-0","journal-title":"Curr Diab Rep"},{"issue":"6","key":"6586_CR9","doi-asserted-by":"publisher","first-page":"e27539","DOI":"10.1016\/j.heliyon.2024.e27539","volume":"10","author":"T Azimi","year":"2024","unstructured":"Azimi T, Johnson J, Campbell SM, Montesanti S (2024) Caregiver burden among parents of children with type 1 diabetes: a qualitative scoping review. Heliyon 10(6):e27539. https:\/\/doi.org\/10.1016\/j.heliyon.2024.e27539","journal-title":"Heliyon"},{"issue":"1","key":"6586_CR10","doi-asserted-by":"publisher","first-page":"68","DOI":"10.2337\/cd22-0073","volume":"41","author":"C Demeterco-Berggren","year":"2022","unstructured":"Demeterco-Berggren C, Ebekozien O, Noor N et al (2022) Factors associated with achieving target A1C in children and adolescents with type 1 diabetes: findings from the T1D exchange quality improvement collaborative. Clin Diabetes 41(1):68\u201375. https:\/\/doi.org\/10.2337\/cd22-0073","journal-title":"Clin Diabetes"},{"issue":"2","key":"6586_CR11","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1089\/dia.2018.0384","volume":"21","author":"NC Foster","year":"2019","unstructured":"Foster NC, Beck RW, Miller KM et al (2019) State of type 1 diabetes management and outcomes from the T1D exchange in 2016\u20132018. Diabetes Technol Ther 21(2):66\u201372. https:\/\/doi.org\/10.1089\/dia.2018.0384","journal-title":"Diabetes Technol Ther"},{"issue":"5","key":"6586_CR12","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.2337\/dc20-1674","volume":"44","author":"R Cardona-Hernandez","year":"2021","unstructured":"Cardona-Hernandez R, Schwandt A, Alkandari H et al (2021) Glycemic outcome associated with insulin pump and glucose sensor use in children and adolescents with type 1 diabetes. Data from the international pediatric registry SWEET. Diabetes Care 44(5):1176\u20131184. https:\/\/doi.org\/10.2337\/dc20-1674","journal-title":"Diabetes Care"},{"issue":"8","key":"6586_CR13","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1111\/pedi.13427","volume":"23","author":"F Sundberg","year":"2022","unstructured":"Sundberg F, deBeaufort C, Krogvold L et al (2022) ISPAD clinical practice consensus guidelines 2022: managing diabetes in preschoolers. Pediatr Diabetes 23(8):1496\u20131511. https:\/\/doi.org\/10.1111\/pedi.13427","journal-title":"Pediatr Diabetes"},{"issue":"8","key":"6586_CR14","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.2337\/db20-0123","volume":"69","author":"LC Foland-Ross","year":"2020","unstructured":"Foland-Ross LC, Tong G, Mauras N et al (2020) Brain function differences in children with type 1 diabetes: a functional MRI study of working memory. Diabetes 69(8):1770\u20131778. https:\/\/doi.org\/10.2337\/db20-0123","journal-title":"Diabetes"},{"issue":"4","key":"6586_CR15","doi-asserted-by":"publisher","first-page":"983","DOI":"10.2337\/dc20-2125","volume":"44","author":"N Mauras","year":"2021","unstructured":"Mauras N, Buckingham B, White NH et al (2021) Impact of type 1 diabetes in the developing brain in children: a longitudinal study. Diabetes Care 44(4):983\u2013992. https:\/\/doi.org\/10.2337\/dc20-2125","journal-title":"Diabetes Care"},{"issue":"8","key":"6586_CR16","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.2337\/dc20-0171","volume":"43","author":"J Suput Omladic","year":"2020","unstructured":"Suput Omladic J, Slana Ozimic A, Vovk A et al (2020) Acute hyperglycemia and spatial working memory in adolescents with type 1 diabetes. Diabetes Care 43(8):1941\u20131944. https:\/\/doi.org\/10.2337\/dc20-0171","journal-title":"Diabetes Care"},{"issue":"10","key":"6586_CR17","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1007\/s11892-014-0533-x","volume":"14","author":"DD Schwartz","year":"2014","unstructured":"Schwartz DD, Wasserman R, Powell PW, Axelrad ME (2014) Neurocognitive outcomes in pediatric diabetes: a developmental perspective. Curr Diab Rep 14(10):533. https:\/\/doi.org\/10.1007\/s11892-014-0533-x","journal-title":"Curr Diab Rep"},{"issue":"1","key":"6586_CR18","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1076\/chin.10.1.36.26241","volume":"10","author":"M Desrocher","year":"2004","unstructured":"Desrocher M, Rovet J (2004) Neurocognitive correlates of type 1 diabetes mellitus in childhood. Child Neuropsychol 10(1):36\u201352. https:\/\/doi.org\/10.1076\/chin.10.1.36.26241","journal-title":"Child Neuropsychol"},{"issue":"4","key":"6586_CR19","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.neuint.2013.06.018","volume":"63","author":"G Languren","year":"2013","unstructured":"Languren G, Montiel T, Julio-Amilpas A, Massieu L (2013) Neuronal damage and cognitive impairment associated with hypoglycemia: an integrated view. Neurochem Int 63(4):331\u2013343. https:\/\/doi.org\/10.1016\/j.neuint.2013.06.018","journal-title":"Neurochem Int"},{"issue":"1","key":"6586_CR20","doi-asserted-by":"publisher","first-page":"236","DOI":"10.2337\/db09-1117","volume":"59","author":"T Hershey","year":"2010","unstructured":"Hershey T, Perantie DC, Wu J, Weaver PM, Black KJ, White NH (2010) Hippocampal volumes in youth with type 1 diabetes. Diabetes 59(1):236\u2013241. https:\/\/doi.org\/10.2337\/db09-1117","journal-title":"Diabetes"},{"key":"6586_CR21","unstructured":"Provention Bio Inc. (2025) Tzield. Highlights of prescribing information. Available from: https:\/\/products.sanofi.us\/tzield\/tzield.pdf. Accessed: 2 Oct 2025"},{"issue":"18","key":"6586_CR22","doi-asserted-by":"publisher","first-page":"e177492","DOI":"10.1172\/JCI177492","volume":"134","author":"A Lledo-Delgado","year":"2024","unstructured":"Lledo-Delgado A, Preston-Hurlburt P, Currie S et al (2024) Teplizumab induces persistent changes in the antigen-specific repertoire in individuals at risk for type 1 diabetes. J Clin Invest 134(18):e177492. https:\/\/doi.org\/10.1172\/JCI177492","journal-title":"J Clin Invest"},{"issue":"583","key":"6586_CR23","doi-asserted-by":"publisher","first-page":"eabc8980","DOI":"10.1126\/scitranslmed.abc8980","volume":"13","author":"EK Sims","year":"2021","unstructured":"Sims EK, Bundy BN, Stier K et al (2021) Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals. Sci Transl Med 13(583):eabc8980. https:\/\/doi.org\/10.1126\/scitranslmed.abc8980","journal-title":"Sci Transl Med"},{"issue":"10","key":"6586_CR24","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.2337\/dc23-0675","volume":"46","author":"KC Herold","year":"2023","unstructured":"Herold KC, Gitelman SE, Gottlieb PA, Knecht LA, Raymond R, Ramos EL (2023) Teplizumab: a disease-modifying therapy for type 1 diabetes that preserves beta-cell function. Diabetes Care 46(10):1848\u20131856. https:\/\/doi.org\/10.2337\/dc23-0675","journal-title":"Diabetes Care"},{"issue":"23","key":"6586_CR25","doi-asserted-by":"publisher","first-page":"2151","DOI":"10.1056\/NEJMoa2308743","volume":"389","author":"EL Ramos","year":"2023","unstructured":"Ramos EL, Dayan CM, Chatenoud L et al (2023) Teplizumab and beta-cell function in newly diagnosed type 1 diabetes. N Engl J Med 389(23):2151\u20132161. https:\/\/doi.org\/10.1056\/NEJMoa2308743","journal-title":"N Engl J Med"},{"issue":"10","key":"6586_CR26","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.2337\/dc22-1960","volume":"46","author":"BI Frohnert","year":"2023","unstructured":"Frohnert BI, Ghalwash M, Li Y et al (2023) Refining the definition of stage 1 type 1 diabetes: an ontology-driven analysis of the heterogeneity of multiple islet autoimmunity. Diabetes Care 46(10):1753\u20131761. https:\/\/doi.org\/10.2337\/dc22-1960","journal-title":"Diabetes Care"},{"issue":"22","key":"6586_CR27","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1056\/NEJMoa012864","volume":"346","author":"KC Herold","year":"2002","unstructured":"Herold KC, Hagopian W, Auger JA et al (2002) Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346(22):1692\u20131698. https:\/\/doi.org\/10.1056\/NEJMoa012864","journal-title":"N Engl J Med"},{"issue":"11","key":"6586_CR28","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.2337\/db13-0345","volume":"62","author":"KC Herold","year":"2013","unstructured":"Herold KC, Gitelman SE, Ehlers MR et al (2013) Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes 62(11):3766\u20133774. https:\/\/doi.org\/10.2337\/db13-0345","journal-title":"Diabetes"},{"issue":"2","key":"6586_CR29","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1007\/s00125-012-2753-4","volume":"56","author":"KC Herold","year":"2013","unstructured":"Herold KC, Gitelman SE, Willi SM et al (2013) Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia 56(2):391\u2013400. https:\/\/doi.org\/10.1007\/s00125-012-2753-4","journal-title":"Diabetologia"},{"issue":"9790","key":"6586_CR30","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/S0140-6736(11)60931-8","volume":"378","author":"N Sherry","year":"2011","unstructured":"Sherry N, Hagopian W, Ludvigsson J et al (2011) Teplizumab for treatment of type 1 diabetes (Protege study): 1-year results from a randomised, placebo-controlled trial. Lancet 378(9790):487\u2013497. https:\/\/doi.org\/10.1016\/S0140-6736(11)60931-8","journal-title":"Lancet"},{"issue":"7","key":"6586_CR31","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1056\/NEJMoa1902226","volume":"381","author":"KC Herold","year":"2019","unstructured":"Herold KC, Bundy BN, Long SA et al (2019) An Anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 381(7):603\u2013613. https:\/\/doi.org\/10.1056\/NEJMoa1902226","journal-title":"N Engl J Med"},{"issue":"Suppl 1","key":"6586_CR32","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.2337\/dc22-S002","volume":"45","author":"American Diabetes Association Professional Practice Committee","year":"2022","unstructured":"American Diabetes Association Professional Practice Committee (2022) 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care 45(Suppl 1):S17\u2013S38. https:\/\/doi.org\/10.2337\/dc22-S002","journal-title":"Diabetes Care"},{"issue":"Supplement_1","key":"6586_CR33","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.2337\/dc25-S002","volume":"48","author":"American Diabetes Association Professional Practice Committee","year":"2025","unstructured":"American Diabetes Association Professional Practice Committee (2025) 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025. Diabetes Care 48(Supplement_1):S27\u2013S49. https:\/\/doi.org\/10.2337\/dc25-S002","journal-title":"Diabetes Care"},{"issue":"3","key":"6586_CR34","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1016\/j.clim.2013.05.001","volume":"149","author":"AG Daifotis","year":"2013","unstructured":"Daifotis AG, Koenig S, Chatenoud L, Herold KC (2013) Anti-CD3 clinical trials in type 1 diabetes mellitus. Clin Immunol 149(3):268\u2013278. https:\/\/doi.org\/10.1016\/j.clim.2013.05.001","journal-title":"Clin Immunol"},{"issue":"11","key":"6586_CR35","doi-asserted-by":"publisher","first-page":"3901","DOI":"10.2337\/db13-0236","volume":"62","author":"W Hagopian","year":"2013","unstructured":"Hagopian W, Ferry RJ Jr, Sherry N et al (2013) Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protege trial. Diabetes 62(11):3901\u20133908. https:\/\/doi.org\/10.2337\/db13-0236","journal-title":"Diabetes"},{"issue":"8","key":"6586_CR36","doi-asserted-by":"publisher","first-page":"889","DOI":"10.2217\/imt-2016-0049","volume":"8","author":"C Kuhn","year":"2016","unstructured":"Kuhn C, Weiner HL (2016) Therapeutic anti-CD3 monoclonal antibodies: from bench to bedside. Immunotherapy 8(8):889\u2013906. https:\/\/doi.org\/10.2217\/imt-2016-0049","journal-title":"Immunotherapy"},{"issue":"2","key":"6586_CR37","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.clim.2009.04.007","volume":"132","author":"KC Herold","year":"2009","unstructured":"Herold KC, Gitelman S, Greenbaum C et al (2009) Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol 132(2):166\u2013173. https:\/\/doi.org\/10.1016\/j.clim.2009.04.007","journal-title":"Clin Immunol"},{"issue":"118","key":"6586_CR38","doi-asserted-by":"publisher","first-page":"118ra112","DOI":"10.1126\/scitranslmed.3003401","volume":"4","author":"F Waldron-Lynch","year":"2012","unstructured":"Waldron-Lynch F, Henegariu O, Deng S et al (2012) Teplizumab induces human gut-tropic regulatory cells in humanized mice and patients. Sci Transl Med 4(118):118ra112. https:\/\/doi.org\/10.1126\/scitranslmed.3003401","journal-title":"Sci Transl Med"},{"issue":"12","key":"6586_CR39","doi-asserted-by":"publisher","first-page":"2121","DOI":"10.1007\/s00125-022-05780-9","volume":"65","author":"A Weiss","year":"2022","unstructured":"Weiss A, Zapardiel-Gonzalo J, Voss F et al (2022) Progression likelihood score identifies substages of presymptomatic type 1 diabetes in childhood public health screening. Diabetologia 65(12):2121\u20132131. https:\/\/doi.org\/10.1007\/s00125-022-05780-9","journal-title":"Diabetologia"},{"issue":"3","key":"6586_CR40","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1007\/s00125-019-05047-w","volume":"63","author":"LM Jacobsen","year":"2020","unstructured":"Jacobsen LM, Bocchino L, Evans-Molina C et al (2020) The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening. Diabetologia 63(3):588\u2013596. https:\/\/doi.org\/10.1007\/s00125-019-05047-w","journal-title":"Diabetologia"},{"issue":"11","key":"6586_CR41","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1007\/s00125-019-4952-8","volume":"62","author":"M Turtinen","year":"2019","unstructured":"Turtinen M, Harkonen T, Parkkola A, Ilonen J, Knip M, Finnish Pediatric Diabetes Register (2019) Characteristics of familial type 1 diabetes: effects of the relationship to the affected family member on phenotype and genotype at diagnosis. Diabetologia 62(11):2025\u20132039. https:\/\/doi.org\/10.1007\/s00125-019-4952-8","journal-title":"Diabetologia"},{"issue":"5","key":"6586_CR42","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.2337\/dc20-1829","volume":"44","author":"B Karges","year":"2021","unstructured":"Karges B, Prinz N, Placzek K et al (2021) A comparison of familial and sporadic type 1 diabetes among young patients. Diabetes Care 44(5):1116\u20131124. https:\/\/doi.org\/10.2337\/dc20-1829","journal-title":"Diabetes Care"},{"issue":"1","key":"6586_CR43","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s13340-015-0212-4","volume":"7","author":"K Sakaguchi","year":"2016","unstructured":"Sakaguchi K, Takeda K, Maeda M et al (2016) Glucose area under the curve during oral glucose tolerance test as an index of glucose intolerance. Diabetol Int 7(1):53\u201358. https:\/\/doi.org\/10.1007\/s13340-015-0212-4","journal-title":"Diabetol Int"}],"container-title":["Diabetologia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06586-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00125-025-06586-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00125-025-06586-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T22:04:15Z","timestamp":1767823455000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00125-025-06586-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["6586"],"URL":"https:\/\/doi.org\/10.1007\/s00125-025-06586-1","relation":{},"ISSN":["0012-186X","1432-0428"],"issn-type":[{"value":"0012-186X","type":"print"},{"value":"1432-0428","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]},"assertion":[{"value":"8 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors would like to thank the participants of the PETITE-T1D trial and their families, as well as the staff members conducting the trial. Medical writing support was provided by A. Perault and A. E. Todd (IMPRINT Science, New York, NY, USA). This work was presented at the 51st Annual Conference of the International Society for Pediatric and Adolescent Diabetes (ISPAD) in Montr\u00e9al, Canada, on 5\u20128 November 2025.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Acknowledgements"}},{"value":"Qualified researchers may request access to data. Further details on Sanofi\u2019s data sharing criteria, eligible studies and process for requesting access can be found at:\n                      \n                      .","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Data availability"}},{"value":"This study and medical writing support were funded by Sanofi. Sanofi designed the study and collected and analysed the data. Sanofi was also involved in interpreting the data, writing the report and approving the report for publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}},{"value":"SEG has served on advisory boards for Abata Therapeutics, Genentech, GentiBio, Eli Lilly, Provention Bio, SAB Biotherapeutics, Sana Biotechnology, Sanofi and Shoreline Biosciences; has received support from the National Institutes for Health (NIH), Provention Bio and Sanofi for roles as an investigator in clinical trials; and serves on data and safety monitoring boards for Diamyd Medical, Breakthrough T1D (formerly known as JDRF) and INNODIA. KS has served on advisory boards for Provention Bio and Sanofi and has received support from the NIH, Breakthrough T1D, Sanofi and Provention Bio for roles as an investigator in clinical trials. JLS consults for Abbott Diabetes, Insulet, Medscape, Medtronic Diabetes, Vertex and Ypsomed; has served on advisory boards for Cecelia Health, Insulet, MannKind, Medtronic Diabetes, StartUp Health T1D Moonshot and Vertex; and has received research support from Abbott Diabetes, Dexcom, Breakthrough T1D, Insulet, Medtronic, NIH and Provention Bio. SBL has consulted for Sanofi. TQ is a consultant for BioMarin, Janssen Research & Development, Merck, Pfizer, Provention Bio and Sanofi and is a Clinical Trial Principal Investigator at the Buffalo site for Ascendis, BioMarin, Janssen, OPKO Biologics, Pfizer, Provention Bio and Sanofi. WER has received grants or contracts from NIH and Provention Bio. BS has consulted for Provention Bio. SMW has received support from NIH, Provention Bio and Sanofi for roles as an investigator in clinical trials. LK, EN, WS and DM are employees of Sanofi and may hold stock in the company. IL is an employee of Cytel and was serving as a vendor to Sanofi at the time of the study. LAD has served on advisory boards for Abata Therapeutics, Tandem and Biomea Fusion; has received research support from NIH, Lilly, MannKind, Provention Bio, Sanofi and Zealand for roles as an investigator in clinical trials; has received study supplies from Dexcom; and serves on data safety monitoring boards for Lilly and Merck for non-diabetes indications.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 relationships and activities"}},{"value":"SEG, SBL, TQ, WER, BS, SMW and LAD contributed to the acquisition and interpretation of data, drafting the article and reviewing the article critically. KS and JLS contributed to the design of the study, acquisition and interpretation of data, drafting the article and reviewing the article critically. LK, EN and DM contributed to the conception and design of the study, acquisition and interpretation of data, drafting the article and reviewing the article critically. IL contributed to the analysis and interpretation of data, drafting the article and reviewing the article critically. WS contributed to the interpretation of data, drafting the article and reviewing the article critically. All authors gave final approval of the version to be published. LK accepts full responsibility for the work and\/or the conduct of the study, had access to the data, and controlled the decision to publish.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Contribution statement"}}]}}