OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of 
teplizumab and evaluate relevant clinical trial data.
DATA SOURCES: Searches of MEDLINE, International Pharmaceutical Abstracts, 
ClinicalTrials.gov, American Diabetes Association scientific posters, and Google 
Scholar (1966-May 2012) were conducted using the key words teplizumab, anti-CD3 
monoclonal antibody, MGA031, and hOKT3γ1 (Ala-Ala). Searches were limited to 
articles published in English.
STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating teplizumab for 
type 1 diabetes mellitus (T1DM) published in English were selected from the data 
sources. All published relevant abstracts were included. References cited in 
identified articles were used for additional citations.
DATA SYNTHESIS: T1DM accounts for up to 10% of all cases of diabetes mellitus. 
T1DM is characterized as a chronic and progressive autoimmune disease leading to 
the destruction of insulin-producing β-cells of the pancreas. Teplizumab is a 
humanized Fc-mutated anti-CD3 monoclonal antibody that alters the function of 
the T-lymphocytes that mediate the destruction of the insulin-producing β-cells. 
While clinical data are limited, both Phase 2 and Phase 3 studies have 
demonstrated preserved C-peptide response as a measure of insulin production, 
decreased exogenous insulin use, and improved glycemic control following a 12- 
to 14-day teplizumab infusion in patients diagnosed with T1DM within the 
previous 6 weeks. However, 1 Phase 3 trial failed to find the same benefits in 
those diagnosed with T1DM within the previous 12 weeks when a lower cumulative 
teplizumab dose was used. Initial studies indicated that teplizumab is well 
tolerated, with a self-limiting rash as the most commonly reported adverse 
effect.
CONCLUSIONS: Teplizumab is an anti-CD3 human monoclonal antibody with promising 
activity in treatment of patients with T1DM. Results from Phase 3 trials are 
needed to further determine safety, efficacy, and dosing frequency.