Teplizumab Delays Type 1 Diabetes Onset by 4 Years in At-Risk Children: Extended Trial Data
Quick Facts
How Long Does Teplizumab Delay Type 1 Diabetes in Children?
The TN-10 trial, coordinated by TrialNet and published in the New England Journal of Medicine in 2019, was the first study to demonstrate that an immunotherapy could delay the onset of type 1 diabetes. The trial enrolled 76 participants aged 8 and older who had stage 2 type 1 diabetes (two or more autoantibodies plus dysglycemia on oral glucose tolerance testing but no clinical symptoms). Participants received either a single 14-day intravenous course of teplizumab (an anti-CD3 monoclonal antibody) or placebo.
The original analysis showed that the median time to clinical diabetes diagnosis was 48.4 months in the teplizumab group compared to 24.4 months in the placebo group — a delay of approximately 2 years (hazard ratio 0.41, 95% CI: 0.22–0.78). Extended follow-up data presented at scientific meetings have shown that the treatment benefit persists and may increase over time, with a proportion of teplizumab-treated participants remaining clinically diabetes-free well beyond the initial 2-year delay. Immune profiling revealed that non-progressors had sustained increases in partially exhausted CD8+ T cells, suggesting durable immune modulation from a single treatment course. Ongoing analysis continues to track long-term outcomes in this cohort.
What Does This Mean for Families With Type 1 Diabetes Risk?
Teplizumab was approved by the FDA in November 2022 under the brand name Tzield, making it the first therapy approved to delay the onset of type 1 diabetes. The extended TN-10 data strengthen the case for screening and early intervention. Major diabetes organizations including JDRF and the Endocrine Society support autoantibody testing for first-degree relatives of people with type 1 diabetes. The TrialNet Pathway to Prevention study offers free autoantibody screening for relatives aged 2.5–45. Currently, approximately 244,000 children and adolescents in the United States have type 1 diabetes, according to CDC estimates.
Dr. Kevan Herold of Yale University, the trial's principal investigator, has emphasized the developmental significance of delaying diabetes onset — years without insulin management during critical school years represent a meaningful quality-of-life benefit for children and families. The treatment cost of Tzield is approximately $194,000 for the 14-day course, which has been a barrier to widespread uptake. Health economics analyses are ongoing to evaluate cost-effectiveness when accounting for delayed insulin therapy costs, reduced diabetic ketoacidosis hospitalizations, and improved long-term glycemic outcomes. A Phase 3 trial (PROTECT) is investigating whether a second teplizumab course can extend the diabetes-free period further, with results anticipated in the coming years.
Frequently Asked Questions
Children with a first-degree relative (parent or sibling) with type 1 diabetes have approximately a 5% lifetime risk compared to about 0.4% in the general population. The TrialNet Pathway to Prevention study offers free autoantibody screening for relatives aged 2.5–45. Two or more positive autoantibodies indicate stage 1 type 1 diabetes with a greater than 90% lifetime progression risk.
The most common side effects include a temporary rash, mild lymphopenia (low lymphocyte count), headache, and transient cytokine release symptoms such as fever and nausea during the infusion period. Most side effects resolve within weeks of treatment completion. In clinical trial follow-up, no long-term immunosuppression or increased serious infection risk was observed.
Current evidence shows teplizumab delays but does not prevent type 1 diabetes in most patients — the majority of treated participants in the TN-10 trial eventually progressed to clinical diabetes. However, a subset of treated individuals remained diabetes-free during extended follow-up, raising the possibility that some may achieve long-term immune tolerance. Research into combination immunotherapies and repeat dosing through the PROTECT trial aims to improve these outcomes.
References
- Herold KC, et al. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. New England Journal of Medicine. 2019;381(7):603-613.
- U.S. Food and Drug Administration. FDA Approves First Drug That Can Delay Onset of Type 1 Diabetes. FDA News Release, November 17, 2022.
- Teplizumab-mzwv (Tzield) prescribing information. Provention Bio/Sanofi. 2022.
- Sims EK, et al. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022;71(4):610-623.