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Aims/hypothesis <p>This is the first real-world prospective observational study of teplizumab use following approval by the United States Food and Drug Administration in individuals with stage 2 type 1 diabetes. We examined whether glycaemic responses observed in controlled trials were reproduced in real-world practice and explored immunological biomarkers associated with treatment.</p> Methods <p>Children and adults with stage 2 type 1 diabetes were prospectively followed in the Early Type 1 Diabetes Clinic at the Barbara Davis Center. Individuals who received teplizumab between April 2023 and February 2025 (<i>n</i>=30) were compared with an untreated group (<i>n</i>=10). Key assessments included OGTTs, HbA<sub>1c</sub> measurements and continuous glucose monitoring (CGM) data, collected before and after treatment. Longitudinal metabolic data were available for up to 22 treated participants, with follow-up assessments occurring between 2 and 13 months after treatment. Changes in Epstein–Barr virus (EBV) and islet antigen-targeting T cell receptor (TCR) β chains were measured longitudinally from genomic DNA via a PCR-based targeted TCR sequencing assay.</p> Results <p>Among treated individuals followed up between 2 and 6 months after treatment, OGTT 2 h glucose improved (10.7 ± 2.1 to 8.8 ± 2.8 mmol/l, <i>p</i>=0.007), as did HbA<sub>1c</sub> (40 ± 4 to 39 ± 6 mmol/mol [5.8 ± 0.4% to 5.7 ± 0.5%], <i>p</i>=0.044). In addition, 67% had a stable or reduced CGM time ≥7.8 mmol/l. CD4 preproinsulin-specific TCRs declined after treatment, with no change in the untreated group. These reductions correlated with higher C-peptide AUC (<i>r</i>=−0.656, <i>p</i>=0.013). EBV TCR sequences were similar before and after teplizumab treatment.</p> Conclusions/interpretation <p>Teplizumab can be safely and effectively administered in clinical practice. Early glycaemic improvements and reductions in CD4 preproinsulin-specific TCRs suggest that post-treatment immunological changes may serve as biomarkers to guide early-stage intervention.</p> Graphical Abstract <p></p>

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Teplizumab treatment for stage 2 type 1 diabetes: a real-world evaluation of metabolic and immunological outcomes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月15日

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  • Kagan E. Karakus,
  • Lexie Chesshir,
  • Sonya Walker,
  • Erin E. Baschal,
  • Kristen A. McDaniel,
  • Taylor M. Triolo,
  • Andrea K. Steck,
  • Brigitte I. Frohnert,
  • Peter A. Gottlieb,
  • Aaron W. Michels,
  • Kimber M. Simmons

摘要

Aims/hypothesis

This is the first real-world prospective observational study of teplizumab use following approval by the United States Food and Drug Administration in individuals with stage 2 type 1 diabetes. We examined whether glycaemic responses observed in controlled trials were reproduced in real-world practice and explored immunological biomarkers associated with treatment.

Methods

Children and adults with stage 2 type 1 diabetes were prospectively followed in the Early Type 1 Diabetes Clinic at the Barbara Davis Center. Individuals who received teplizumab between April 2023 and February 2025 (n=30) were compared with an untreated group (n=10). Key assessments included OGTTs, HbA1c measurements and continuous glucose monitoring (CGM) data, collected before and after treatment. Longitudinal metabolic data were available for up to 22 treated participants, with follow-up assessments occurring between 2 and 13 months after treatment. Changes in Epstein–Barr virus (EBV) and islet antigen-targeting T cell receptor (TCR) β chains were measured longitudinally from genomic DNA via a PCR-based targeted TCR sequencing assay.

Results

Among treated individuals followed up between 2 and 6 months after treatment, OGTT 2 h glucose improved (10.7 ± 2.1 to 8.8 ± 2.8 mmol/l, p=0.007), as did HbA1c (40 ± 4 to 39 ± 6 mmol/mol [5.8 ± 0.4% to 5.7 ± 0.5%], p=0.044). In addition, 67% had a stable or reduced CGM time ≥7.8 mmol/l. CD4 preproinsulin-specific TCRs declined after treatment, with no change in the untreated group. These reductions correlated with higher C-peptide AUC (r=−0.656, p=0.013). EBV TCR sequences were similar before and after teplizumab treatment.

Conclusions/interpretation

Teplizumab can be safely and effectively administered in clinical practice. Early glycaemic improvements and reductions in CD4 preproinsulin-specific TCRs suggest that post-treatment immunological changes may serve as biomarkers to guide early-stage intervention.

Graphical Abstract