Clinical trial evidence for disease-modifying therapies across the type 1 diabetes continuum: from presymptomatic stages to recent-onset disease.

Abstract

Type 1 diabetes (T1D) can be identified before symptomatic insulin deficiency, creating an opportunity to intervene while meaningful beta-cell function remains. PubMed/MEDLINE and Clinical Trials.gov were searched for randomized trials, follow-up reports, and real-world studies published from January 2000 to August 2026; regulatory documents, and major guidelines were also reviewed. This article examines disease-modifying therapies in stage 1, stage 2, and recent-onset stage 3 T1D, distinguishing delay of clinical diagnosis from preservation of C-peptide after diagnosis and evaluating efficacy, safety, durability, treatment burden, and implementation. Teplizumab establishes that a finite immunotherapy course can delay progression from stage 2 to stage 3 T1D, but it does not prevent disease. Other approaches demonstrate biological activity, although durable patient-important benefits remain uncertain. Future trials should prioritize comparable clinical outcomes, candidate selection, access, and rigorous evaluation of retreatment, sequential therapy, and mechanism-based combinations.