AIMS/HYPOTHESIS: Type 1 diabetes results from a chronic autoimmune process 
continuing for years after presentation. We tested whether treatment with 
teplizumab (a Fc receptor non-binding anti-CD3 monoclonal antibody), after the 
new-onset period, affects the decline in C-peptide production in individuals 
with type 1 diabetes.
METHODS: In a randomised placebo-controlled trial we treated 58 participants 
with type 1 diabetes for 4-12 months with teplizumab or placebo at four academic 
centres in the USA. A central randomisation centre used computer generated 
tables to allocate treatments. Investigators, patients, and caregivers were 
blinded to group assignment. The primary outcome was a comparison of C-peptide 
responses to a mixed meal after 1 year. We explored modification of treatment 
effects in subgroups of patients.
RESULTS: Thirty-four and 29 subjects were randomized to the drug and placebo 
treated groups, respectively. Thirty-one and 27, respectively, were analysed. 
Although the primary outcome analysis showed a 21.7% higher C-peptide response 
in the teplizumab-treated group (0.45 vs 0.371; difference, 0.059 [95% CI 0.006, 
0.115] nmol/l) (p = 0.03), when corrected for baseline imbalances in HbA(1c) 
levels, the C-peptide levels in the teplizumab-treated group were 17.7% higher 
(0.44 vs 0.378; difference, 0.049 [95% CI 0, 0.108] nmol/l, p = 0.09). A greater 
proportion of placebo-treated participants lost detectable C-peptide responses 
at 12 months (p = 0.03). The teplizumab group required less exogenous insulin 
(p < 0.001) but treatment differences in HbA(1c) levels were not observed. 
Teplizumab was well tolerated. A subgroup analysis showed that treatment 
benefits were larger in younger individuals and those with HbA(1c) <6.5% at 
entry. Clinical responders to teplizumab had an increase in circulating CD8 
central memory cells 2 months after enrolment compared with non-responders.
CONCLUSIONS/INTERPRETATIONS: This study suggests that deterioration in insulin 
secretion may be affected by immune therapy with teplizumab after the new-onset 
period but the magnitude of the effect is less than during the new-onset period. 
Our studies identify characteristics of patients most likely to respond to this 
immune therapy.
TRIAL REGISTRATION: ClinicalTrials.gov NCT00378508
FUNDING: This work was supported by grants 2007-502, 2007-1059 and 2006-351 from 
the JDRF and grants R01 DK057846, P30 DK20495, UL1 RR024139, UL1RR025780, UL1 
RR024131 and UL1 RR024134 from the NIH.