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Cited by 247Diabetes and associated disordersDiabetes Management and ResearchT-cell and B-cell Immunology

Teplizumab Preserves C-Peptide in Recent-Onset Type 1 Diabetes

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Hagopian, William, Ferry, Robert J., Sherry, Nicole, Carlin, David, Bonvini, Ezio, Johnson, Syd, Stein, Kathryn E., Koenig, Scott +4 more·2013·Diabetes
DOI 10.2337/db13-0236PMC PMC3806608
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Abstract

Protégé was a phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years of follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean area under the curve (AUC), a prespecified secondary end point, at 2 years versus placebo. In analyses of prespecified and post hoc subsets at entry, U.S. residents, patients with C-peptide mean AUC >0.2 nmol/L, those randomized ≤6 weeks after diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4 units/kg/day, and 8–17 years of age each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Antidrug antibodies developed in some patients, without apparent change in drug efficacy. No new safety or tolerability issues were observed during year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.

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  • The earlier Protégé trial did not meet its primary composite endpoint of a significant difference in insulin dose and HbA1c at 1 year; however, teplizumab treatment reduced the loss of C-peptide response to a standard mixed meal at 2 years.

    “The earlier Protégé trial, 33,34 which included children and adults, did not meet its primary composite endpoint of a significant difference in the insulin dose and glycated haemoglobin (HbA₁ c ) concentrations at 1 year; however, teplizumab treatment reduced the loss of Cpeptide response to a standard mixed meal, a prespecified secondary endpoint, at 2 years.34”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [34]

  • Teplizumab has shown promise in preserving insulin secretion in stage 3 type 1 diabetes.

    “Although currently being considered but not yet approved for stage 3 type 1 diabetes, teplizumab has shown promise in preserving insulin secretion (table 1).”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [34]

  • Post-hoc analyses identified subgroups with higher baseline C-peptide, lower insulin use, lower HbA1c, younger age, and shorter time since diagnosis who benefited most from teplizumab treatment, suggesting greater efficacy with early treatment in paediatric populations.

    “Posthoc analyses identified subgroups with higher baseline Cpeptide measurement, lower insulin use, lower HbA₁ C , younger age, and shorter time since diagnosis who benefited most from teplizumab treatment, suggesting greater efficacy with early treatment in paediatric populations.34”

    From The future of type 1 diabetes therapy (2025) · cites this paper as [34]

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Research works printed but not linked: 25

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Authors
Hagopian, W., Ferry, R. J., Sherry, N., Carlin, D., Bonvini, E., Johnson, S., Stein, K. E., Koenig, S., Daifotis, A. G., Herold, K. C., Ludvigsson, J., & for the Protégé Trial Investigators
Affiliations
  • Pacific Northwest Research Institute (US)
  • University of Tennessee Health Science Center (US)
  • Massachusetts General Hospital (US)
  • MacroGenics (United States) (US)
  • Yale University (US)
  • Linköping University (SE)
Corresponding author
Hagopian, William
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2013-10-18
Volume
62
Issue
11
Pages
3901-3908
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db13-0236
PMC
PMC3806608
OpenAlex
W2124812894
Cited by
247
References
5
Citations by year
2026: 7 · 2025: 19 · 2024: 24 · 2023: 29 · 2022: 21 · 2021: 18 · 2020: 22 · 2019: 12 · 2018: 17 · 2017: 15 · 2016: 18 · 2015: 25 · 2014: 11 · 2013: 8
FWCI
13.71
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (U01DK085465, T35DK007405)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R21HD059292)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
teplizumab, type 1 diabetes, recent-onset type 1 diabetes, anti-CD3 therapy, immunotherapy, antidrug antibodies, predictors of treatment response, HbA1c, pediatric patients
MeSH terms
Adolescent, C-Peptide, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Drug Administration Schedule, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Immunotherapy, Insulin, Placebos, Area Under Curve, Antibodies, Monoclonal, Humanized

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