Teplizumab for Delaying Type 1 Diabetes Onset
Teplizumab should be offered to individuals aged ≥8 years with stage 2 type 1 diabetes to delay progression to symptomatic stage 3 disease, administered as a 14-day intravenous infusion course in a specialized setting with trained personnel. 1
Patient Selection Criteria
You should consider teplizumab for patients who meet ALL of the following criteria:
Clinical Efficacy
The evidence supporting teplizumab is compelling:
- Median time to stage 3 diagnosis doubled from 24.4 months (placebo) to 48.4 months (teplizumab), with hazard ratio 0.41 (95% CI 0.22-0.78) 1, 5
- At 2 years, only 43% of teplizumab-treated patients progressed to stage 3 versus 72% of placebo patients 1, 3
- Annualized progression rates were 14.9% per year with teplizumab versus 35.9% per year with placebo 5
Predictors of Superior Response
Certain genetic and antibody profiles predict better outcomes with teplizumab:
- Absence of HLA-DR3: HR 0.18 (95% CI 0.07-0.45) 1
- Presence of HLA-DR4: HR 0.20 (95% CI 0.09-0.45) 1
- Absence of anti-ZnT8 antibody: HR 0.07 (95% CI 0.02-0.26) 1, 3
Administration Protocol
Teplizumab requires careful administration:
- 14-day intravenous infusion course given as a single treatment 1, 2
- BSA-based dosing to normalize exposure across body weights 2
- Must be administered in a facility with personnel trained in managing infusion reactions and immune-mediated adverse events 4
Safety Profile
The most common adverse reactions are manageable but require monitoring:
- Transient lymphopenia in 73% of patients, with nadir on day 5 of the 14-day course 1, 2
- Rash in 36% of patients 1
- Headache, gastrointestinal symptoms, and mild cytokine release syndrome occur during infusion 6
- Anti-teplizumab antibodies develop in approximately 57% of patients, with 46% developing neutralizing antibodies 2
- Higher incidence of rash in patients who develop anti-drug antibodies 2
Critical Contraindications
Do not use teplizumab in patients with newly diagnosed type 1 diabetes (stage 3) who already have symptoms and are on insulin therapy, as it is FDA-approved exclusively for stage 2 disease 3, 2
Special Populations
- Pediatric patients <8 years: Safety and effectiveness not established 2
- Pregnancy: No human data available; maternal IgG crosses the placenta 2
- Lactation: Women may interrupt breastfeeding and pump and discard breast milk during treatment and for 20 days after administration 2
Practical Implementation
When discussing teplizumab with eligible patients or caregivers:
- The primary benefit is delaying progression to symptomatic diabetes, providing more time before insulin dependence 1, 5
- Real-world survey data shows 87% of recipients felt grateful for the opportunity, 72% believed it would slow disease progression, and >80% would recommend it to others in similar situations 7
- Patients should be counseled about diabetes symptoms and DKA prevention regardless of treatment decision 1
Guideline Authority
The American Diabetes Association's 2025 Standards of Care (Recommendation 3.15) provides the most current guideline recommendation for teplizumab use 1, representing an update from the 2022 guidelines when the drug was still under FDA review 1.