Introduction and Objective: Teplizumab delays progression from stage 2 to stage 3 type 1 diabetes, but real-world practice differs from trials and may treat individuals closer to stage 3. We assessed insulin initiation/discontinuation during and after teplizumab, stage 3-free survival, and insulin requirements among those who progressed. Methods: IRB-approved prospective observational cohort of individuals treated with teplizumab at a single center (April 2023-August 2025). Stage 2 eligibility reflected clinical practice; dysglycemia was documented by OGTT or other glycemic measures when OGTT was unavailable. Insulin use during the 14-day infusion course and early post-infusion discontinuation were recorded. Participants were followed for progression to stage 3; Kaplan-Meier diabetes-free survival was estimated. Among progressors with follow-up, insulin dose (units/kg/day), CGM metrics, and HbA1c were summarized. Results: Forty-one individuals completed teplizumab; 8/41 (20%) initiated insulin during infusion and 5/8 discontinued after a mean of 15 days (range 8-27). Among 35 individuals followed a median of 13.5 months, 9/35 (36%) progressed to stage 3 at 9±8 months post-infusion (range 0.1-28.1). Kaplan-Meier estimates showed diabetes-free survival of 84% at 12 months and 57% at 2 years (8/14 at risk). In progressors with post-diagnosis data (n=7; 2.5-25.9 months since diagnosis), total daily insulin dose ranged 0-0.52 units/kg/day (median 0.19; IQR 0.13-0.23) with time-in-range 73-97%, minimal hypoglycemia (0-1% time 70 mg/dL), and HbA1c 5.3-6.8%. Conclusion: In this prospective real-world teplizumab cohort, insulin initiation during infusion occurred in one-fifth of patients and was usually transient. Despite heterogeneous baseline dysglycemia, stage 3-free survival aligned with trial benchmarks. Among those who progressed, insulin requirements were often very low with in target CGM and HbA1c, highlighting the potential for clinically meaningful benefit beyond delayed diagnosis. Disclosure K. Simmons: None. L. Chesshir: Advisory Panel; Current; Sanofi. J. Stoughton: None. H. O'Donnell: Consultant; Current; Sanofi. Advisory Panel; Ended; Sanofi. Stock/Shareholder; Current; Eli Lilly and Company, Johnson Current; Sanofi. B. Frohnert: None. P. Gottlieb: Consultant; Current; Eli Lilly and Company. Board Member; Current; IM Therapeutics. Other - CEO, CMO; Current; IM Therapeutics. Research Support; Current; Immune Tolerance Network, Nova Laboratories, National Institute of Diabetes and Digestive and Kidney Diseases. Advisory Panel; Current; Sanofi. Research Support; Current; Sanofi. Consultant; Current; SAB Biotherapeutics, Inc., Anaptys Bio, Cour, T1D Fund. Consultant; Ended; Imcyse, Viacyte, Abata. Funding Breakthrough T1D (3-SRA-2023-1348-S-B)
SIMMONS et al. (Fri,) studied this question.