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

Two-Year Results From the Randomized, Placebo-Controlled Protégé Trial

  1. for the Protégé Trial Investigators*
  1. 1Pacific Northwest Diabetes Research Institute, Seattle, Washington
  2. 2Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children’s Hospital and University of Tennessee Health Science Center, Memphis, Tennessee
  3. 3Department of Pediatrics, Massachusetts General Hospital, Boston, Massachusetts
  4. 4MacroGenics, Rockville, Maryland
  5. 5Departments of Immunobiology and Internal Medicine, Yale University, New Haven, Connecticut
  6. 6Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
  1. Corresponding author: William Hagopian, wah{at}


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.


  • Received February 13, 2013.
  • Accepted June 18, 2013.

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  1. Diabetes vol. 62 no. 11 3901-3908
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