ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This double-blind, multicenter trial randomized 328 children and adolescents (8-17 years-old) diagnosed with type 1 diabetes (T1D) within the past 6 weeks to receive either teplizumab or placebo for two 12-day courses. Teplizumab increased stimulated C-peptide levels after 1.5 years, indicating better preservation of β-cell function.

Teplizumab is a monoclonal antibody that binds to CD3 on the surface of T-cells, thereby reducing the immune response that leads to the destruction of pancreatic β cells. In November 2022, the U.S. Food and Drug Administration approved Teplizumab to delay the onset of stage 3 T1D (clinically manifested T1D) in asymptomatic individuals (≥8 years-old) with stage 2 T1D (≥2 islet auto antibodies and dysglycemia) (1). Approval was granted based on a phase 2 trial where Teplizumab, administered in one 14-day course, delayed the progression from stage 2 to stage 3 T1D by 32.5 months and improved β-cell function in high-risk relatives of individuals with T1D (2).

The current findings, along with those from other similar trials, support teplizumab as a promising and safe disease-modifying therapy for newly diagnosed stage 3 T1D (3). Common adverse events included lymphopenia, rash, and headache, which occurred primarily during or after the first few weeks of teplizumab administration and were self-limited. Of note, there was no difference in other endpoints, such as HbA1c, insulin requirements, time in target glucose range and clinically relevant hypoglycemic events.

This study highlights the importance of early interventions in T1D. Administering teplizumab soon after diagnosis maximizes its potential benefits, aligning with the concept that T1D is a progressive condition that can be altered by early treatment. Early use of immunomodulatory therapies may become a standard component of T1D management.

Limitations are the lack of racial diversity in the study population and the relatively low rate of ketoacidosis than is typical in newly diagnosed T1D (4). Future research should optimise treatment protocols, explore combination therapies, and investigate the long-term impact of β-cell preservation on diabetes complications. Translation of these findings into clinical practice will require careful consideration of safety, patient selection, and long-term efficacy.

References: 1. Keam SJ. Teplizumab: First Approval. Drugs 2023;83:439-4452. Herold KC, Bundy BN, Long SA, et al. An anti-CD3 antibody, teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 2019; 381: 603-13.3. Kamrul-Hasan ABM, Mondal S, et al. Role of Teplizumab, a Humanized Anti-CD3 Monoclonal Antibody, in Managing Newly Diagnosed Type 1 Diabetes: An Updated Systematic Review and Meta-Analysis. Endocr Pract. 2024;30:431-40.4. Piccini B, Schwandt A, Jefferies C, Kordonouri O, Limbert C et al. Association of diabetic ketoacidosis and HbA1c at onset with year-three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry. Pediatr Diabetes. 2020; 21(2):339-48.