Teplizumab Shows Promise in Preserving Beta-Cells in Early Type 1 Diabetes: PROTECT Trial Results

In a recent study, researchers have found that early administration of teplizumab, marketed as Tzield, may help preserve beta-cells in individuals recently diagnosed with Type 1 Diabetes (T1D). The findings from the randomised PROTECT trial reveal encouraging results that could potentially impact the management of this autoimmune disease.

This study was published in The New England Journal Of Medicine by Eleanor Ramos and colleagues. The PROTECT trial enrolled 328 patients between the ages of 8 and 17, who were recently diagnosed with clinical-stage 3 T1D. These patients were randomly assigned to receive teplizumab or a placebo for two 12-day courses, spaced 26 weeks apart. The primary objective was to determine the drug's effect on the preservation of beta-cell function and C-peptide levels in these patients.

Key Findings:

• Beta-Cell Preservation: Individuals who received two courses of teplizumab experienced a 59.3% reduction in the loss of beta-cell function compared to those who received a placebo. The teplizumab group showed higher stimulated C-peptide levels at week 78, with a statistically significant least-squares mean difference of 0.13 pmol/mL (95% CI 0.09-0.17, P<0.001).
• Peak C-Peptide Maintenance: An impressive 94.9% of teplizumab recipients maintained peak C-peptide levels at or above 0.2 pmol/mL, a significant improvement compared to the 79.2% in the placebo group.
  
• Challenges in Lifestyle and Disease Management: Despite these promising results in preserving beta-cell function, the study did not find a measurable benefit in insulin dose requirements, glucose control, or a reduction in hypoglycemia events. The burden of the disease and the patient's overall quality of life did not appear to change significantly as a result of the treatment.
  

The PROTECT trial's results indicate that teplizumab could offer a viable approach to preserving beta-cell function in individuals recently diagnosed with T1D. The observed benefits in maintaining C-peptide levels are significant as they are associated with improved long-term outcomes. While the treatment did not lead to improved disease management or a reduction in insulin requirements, it represents a crucial step in addressing the autoimmune attack on beta-cells in T1D.

Teplizumab, approved in 2022 for individuals with preclinical T1D, has opened new avenues for the management of T1D by targeting the autoimmune response. Challenges remain in identifying candidates who are at the right stage of the disease for the treatment to be effective and ensuring close monitoring and control during the first year post-diagnosis. Further real-world pragmatic studies may help address these questions and expand the use of teplizumab in clinical practice.

Reference:

Ramos, E. L., Dayan, C. M., Chatenoud, L., Sumnik, Z., Simmons, K. M., Szypowska, A., Gitelman, S. E., Knecht, L. A., Niemoeller, E., Tian, W., & Herold, K. C. Teplizumab and β-cell function in newly diagnosed type 1 diabetes. The New England Journal of Medicine,2023. https://doi.org/10.1056/nejmoa2308743