The future of type 1 diabetes therapy

Abstract

The treatment of type 1 diabetes is entering a transformative era.Teplizumab, the first immunotherapy treatment to delay the onset of clinical type 1 diabetes, has been approved by the US Food and Drug Administration.Other immunebased therapies show promise in preserving -cell function.Public health screening using islet autoantibodies is expanding, enabling earlier diagnosis, reducing diabetic ketoacidosis, and allowing timely introduction of diseasemodifying treatments before the need for insulin therapy.-cell replacement is shifting from traditional transplantation of organ donor islets and the pancreas to stem cell-derived cells.Bioengineering methods, such as encapsulation, and gene editing to create hypoimmune cells could reduce the need for immunosuppression that has hampered -cell replacement, and patient-derived stem cells open doors to personalised therapies.Although these innovations have been made available to a small number of patients, scaling them to widespread use remains a challenge.Meanwhile, glucose regulation is improving through the use of automated insulin delivery systems that combine glucose monitoring with insulin pumps.New-generation insulins (those that are ultrarapid, ultralong, and glucose-responsive) improve outcomes by minimising blood sugar fluctuations.Together, these breakthroughs offer renewed hope for improving long-term management and quality of life for people living with type 1 diabetes. Search strategy and selection criteriaWe searched PubMed between Jan 1, 2000, and June 21, 2025 using both MeSH and free-text terms to identify relevant articles.The search focused on terms such as "type 1 diabetes AND", "disease-modifying therapy", "immunotherapy", "adjunct therapies", "anti-CD3", "JAK-inhibitor", "baricitinib", "ATG", "rituximab", "anti-TNF", "IL-2", "DCCT", "C-peptide preservation", "verapamil", "Diamyd", "IL-23", "antigen-based therapy", "CTLA-4", "vaccination", "islet transplantation", "stem cell therapy", "embryonic stem cells", "Vertex-880 cells", "pluripotent stem cells", "insulin", "AID", "diabetes technology", "adjunctive treatment AND insulin", "smart insulin", and "glucose responsive insulin" (appendix pp 1-2).We reviewed guidelines for staging and diagnosing type 1 diabetes published by the American Diabetes Association, the European Association for the Study of Diabetes, and International Society for Pediatric and Adolescent Diabetes.To identify additional eligible studies and trial information, we also searched ClinicalTrials.govand EudraCT.Additional articles were identified via previous familiarity of the authors.Publications were selected on the basis of their level of evidence, clinical relevance, contribution to the field, originality, and recency of publication.Preference was given to articles published in journals with robust policies on conflict of interest and stringent peer-review standards.Only publications in English were considered.This Review explores these three paradigmshifting developments in depth, as each is poised to transform type 1 diabetes treatment.

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