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Despite this progress, major hurdles remain in moving toward personalized medicine approaches for T1D. Here, we highlight the examples of heterogeneity in therapeutic responses to recent beta cell and immune interventions and what these studies can teach us about how to tailor therapy for maximizing benefit to patients at risk of or living with T1D. We examine the differences between proposed endotypes, such as childhood\u2010onset versus adult\u2010onset disease, and how these distinctions may inform the use of different therapies. We also explore the importance of disease staging in determining therapeutic windows, as early interventions appear most effective before extensive beta cell loss. Emerging biomarkers including autoantibody profiles, metabolic indices, and circulating nucleic acids offer additional tools for stratifying patients and predicting responses. Ultimately, recognizing and leveraging patient heterogeneity provides an opportunity to align therapies with underlying physiology, moving beyond \u2018one\u2010size\u2010fits all\u2019 approaches. The promise of personalized T1D therapy will be realized by surmounting the barriers to implementation, including trial design, paediatric underrepresentation, and cost.<\/jats:p>","DOI":"10.1111\/dom.70711","type":"journal-article","created":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:12:53Z","timestamp":1774930373000},"page":"4529-4545","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Toward Personalized Medicine in Type 1 Diabetes: Understanding How Patient Heterogeneity Influences Therapeutic Efficacy"],"prefix":"10.1111","volume":"28","author":[{"given":"Jasmine","family":"Pipella","sequence":"first","affiliation":[{"name":"Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme Children's Hospital Research Institute of Manitoba  Winnipeg Manitoba Canada"},{"name":"Department of Physiology &amp; Pathophysiology Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6851-8899","authenticated-orcid":false,"given":"Peter J.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Diabetes Research Envisioned and Accomplished in Manitoba (DREAM) Research Theme Children's Hospital Research Institute of Manitoba  Winnipeg Manitoba Canada"},{"name":"Department of Physiology &amp; Pathophysiology Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2023.06.018"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.16"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)91943-4"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1902226"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc8980"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-1419"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101365"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000548"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/db17-1006"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2337\/dbi21-0036"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1212716"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00151.2021"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00985-4"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11892-025-01594-2"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.2337\/dbi25-0011"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db24-0439"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.932086"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-023-00853-0"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc21-1251"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0880"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-024-01046-z"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42581-z"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.15155"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1644-9"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A2142"},{"key":"e_1_2_13_27_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041593","article-title":"The Role of B Lymphocytes in Type 1 Diabetes","volume":"15","author":"Smith M. 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