{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:27:32Z","timestamp":1790908052380,"version":"4.1.0"},"reference-count":83,"publisher":"American Diabetes Association","issue":"3","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>The worldwide incidence of type 1 diabetes continues to rise at an alarming rate. One hundred years after the introduction of insulin, the long-entertained hope of moving from symptomatic treatment to disease-modifying therapies is finally taking shape with regulatory approval of teplizumab to delay the onset of stage 3 disease. Here we review teplizumab\u2019s mechanism of action, setting it against the background of emerging disease-modifying therapies for clinical practice, in language accessible to practicing clinicians. A clinical diagnosis of type 1 diabetes and insulin dependence results from progressive autoimmune destruction of pancreatic \u03b2-cells as part of a complicated dialogue between the immune system and the islet. Infusion with teplizumab, a humanized monoclonal antibody that binds the \u03b5-chain of the T lymphocyte CD3 molecule, delays progression from stage 2 to clinical stage 3 type 1 diabetes by almost 3 years. The mechanism of action of teplizumab involves partial agonistic signaling via CD3\/TCR and subsequent deactivation, promoting exhaustion of pancreatic \u03b2-cell-reactive CD8+ T lymphocytes and induction of regulatory T lymphocytes, thereby restoring self-tolerance. With regulatory approval of this agent, clinical practice has entered a new era for treating people with type 1 diabetes, in which disease modification can become the new standard of care. Implementation of global screening for autoantibodies and dysglycemia is underway, enabling efforts to intervene during asymptomatic stages of the disease before insulin treatment is required.<\/jats:p>","DOI":"10.2337\/dci25-0066","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T16:40:02Z","timestamp":1762447202000},"page":"365-374","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":19,"title":["Toward Disease-Modifying Therapies in Type 1 Diabetes: Focus on Teplizumab"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6099-2406","authenticated-orcid":false,"given":"Chantal","family":"Mathieu","sequence":"first","affiliation":[{"name":"Endocrinology, KU Leuven 1 , Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-954X","authenticated-orcid":false,"given":"Emily K.","family":"Sims","sequence":"additional","affiliation":[{"name":"Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine 2 , Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucienne","family":"Chatenoud","sequence":"additional","affiliation":[{"name":"Paris Descartes University 3 , Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-5729","authenticated-orcid":false,"given":"Eddie A.","family":"James","sequence":"additional","affiliation":[{"name":"Translational Research Program, Benaroya Research Institute at Virginia Mason 4 , Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8489-4782","authenticated-orcid":false,"given":"Mark A.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"University of Florida 5 , Gainesville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1534-6613","authenticated-orcid":false,"given":"Kevan C.","family":"Herold","sequence":"additional","affiliation":[{"name":"Department of Immunobiology, Yale University 6 , New Haven, CT"},{"name":"Department of Internal Medicine, Yale University 7 , New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"key":"2026061811430260200_B1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1001\/jama.2014.16425","article-title":"Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010","volume":"313","author":"Livingstone","year":"2015","journal-title":"JAMA"},{"key":"2026061811430260200_B2","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.2337\/db05-1423","article-title":"The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience","volume":"55","author":"Pambianco","year":"2006","journal-title":"Diabetes"},{"key":"2026061811430260200_B3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1089\/dia.2019.0398","article-title":"Estimated lifetime economic burden of type 1 diabetes","volume":"22","author":"Sussman","year":"2020","journal-title":"Diabetes Technol Ther"},{"key":"2026061811430260200_B4","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1055\/s-0044-102090","article-title":"Incidence of diabetic ketoacidosis of new-onset type 1 diabetes in children and adolescents in different countries correlates with human development index (HDI): an updated systematic review, meta-analysis, and meta-regression","volume":"50","author":"Gro\u00dfe","year":"2018","journal-title":"Horm Metab Res"},{"key":"2026061811430260200_B5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.2337\/dc19-0428","article-title":"Diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado children, 2010\u20132017","volume":"43","author":"Alonso","year":"2020","journal-title":"Diabetes Care"},{"key":"2026061811430260200_B6","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.2337\/dc20-0389","article-title":"Increase in prevalence of diabetic ketoacidosis at diagnosis among youth with type 1 diabetes: the SEARCH for Diabetes in Youth Study","volume":"44","author":"Jensen","year":"2021","journal-title":"Diabetes Care"},{"key":"2026061811430260200_B7","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.2337\/dc24-S006","article-title":"6. 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