Teplizumab Shown to Delay Onset of Type 1 Diabetes

The introduction of teplizumab (Tzield®) marks a pivotal development in the therapeutic approach to presymptomatic type 1 diabetes (T1D), particularly for pediatric patients identified in stage 2 disease. With the FDA approval in November 2022 for individuals ≥8 years of age with stage 2 T1D, providers now have the first disease modifying therapy capable of delaying the onset of stage 3 T1D by a median exceeding 2.5 years.

For pediatric endocrinologists, the availability of teplizumab underscores both the expanding importance of early immunologic screening and the need to build clinical infrastructure capable of managing patients across the T1D staging continuum.

Mechanism of Action

Teplizumab is an anti CD3 monoclonal antibody that modulates T cell function through partial agonism and induction of T cell exhaustion. Its effects include:

• Decreased autoreactive T cell activity
• Favorable shifts in the T cell regulatory profile
• Transient lymphopenia followed by repopulation with more tolerogenic cell subsets

In stage 2 T1D—characterized by dysglycemia in the setting of multiple islet autoantibodies—the immunologic environment appears particularly responsive to CD3 directed therapy.

Administration consists of 14 consecutive daily IV infusions, each approximately 30 minutes, requiring infusion center infrastructure and close AE monitoring (e.g., cytokine release symptoms, rash, lymphopenia).

Staging Framework for T1D

The contemporary staging model remains essential for identifying appropriate candidates:

• Stage 1: Normoglycemia + ≥2 islet autoantibodies; asymptomatic
• Stage 2: Dysglycemia + ≥2 autoantibodies; asymptomatic
• Stage 3: Clinical diagnosis with symptomatic hyperglycemia

Teplizumab is indicated exclusively for stage 2, a stage that is currently identified predominantly through family-based or research-based screening programs rather than routine pediatric practice.

Evidence Base

The pivotal TN 10 study demonstrated that a single 14-day course of teplizumab significantly delayed progression to stage 3 T1D:

• Original New England Journal of Medicine publication: median delay ~24 months
• Updated follow up analyses: median delay extended to 32.5 months
• Within 1 year of randomization:
• Placebo: 8 participants progressed
• Teplizumab: 0 participants progressed

The magnitude and consistency of delay highlight that beta cell function can be preserved when immune modulation is initiated prior to overt metabolic decompensation.

Current Eligibility and Ongoing Investigations

FDA approval applies to:

• Studies have been completed to investigate the ability to use Teplizumab down to 1 year of age and it has been shown to be safe. An application is currently at the FDA for possible expansion down to age 1 year.

Ongoing trials are examining:

• Safety and efficacy in stage 3 T1D
• Safety and efficacy in children <8 years
• Repeat dosing protocols
• Combinatorial strategies with other immunomodulators, incretin based therapies, or metabolic agents

Pathways to Stage 1 and Stage 2 Identification

Because only screened individuals can be diagnosed with stage 1 or stage 2 T1D, access to testing remains a central factor. Current screening avenues include:

• Pediatrician ordered antibody testing, particularly for first-degree relatives
• TrialNet, offering in-clinic, lab-based, and at-home kits for relatives
• ASK Program, which provides population level screening for U.S. children ages 1–17

As screening expands, pediatric endocrinologists will increasingly encounter presymptomatic patients requiring longitudinal follow up and counseling.

Who Should Be Screened?

Recommendations continue to evolve, but current groups of interest include:

• First-degree relatives of individuals with T1D
• Children with an autoimmune condition (ex celiac disease, hypothyroidism)
• Children with a first degree relative with an autoimmune condition
• Siblings of pediatric patients with established T1D
• Populations participating in broader public health screening initiatives

Emerging cost-effectiveness data may ultimately shift screening from a targeted to a more universal model.

Clinical Significance of Delaying Stage 3 Onset

For pediatric patients, delaying progression to symptomatic diabetes offers multiple potential benefits:

• Prolongation of endogenous insulin production, reducing glycemic excursions and risk of DKA
• Delay in burden of lifelong insulin therapy
• Preservation of beta cell function, which correlates with improved long-term metabolic outcomes
• Opportunity for structured diabetes education prior to onset
• Potential reduction in lifetime microvascular and macrovascular complications

From a systems perspective, delayed onset may shift initial diagnosis away from acute care settings and reduce rates of DKA at presentation.

Implications for the Future of Disease Modifying Therapy in T1D

Teplizumab likely represents the beginning—not the culmination—of presymptomatic therapeutic strategies. Key unanswered questions relevant to subspecialists include:

• Can serial courses of teplizumab provide cumulative benefit?
• What combination therapies (e.g., CTLA 4 agents, B cell depletion, GLP 1 agonists) may synergize with anti CD3 therapy?
• Which biomarkers best predict response or identify optimal timing?
• How should presymptomatic T1D clinics be structured to support longitudinal monitoring?

As research evolves, pediatric endocrinology will increasingly integrate immunotherapy alongside traditional metabolic management.

Institutional Readiness

The Division of Diabetes and Endocrinology at Cincinnati Children’s is prepared to evaluate and treat eligible patients with teplizumab. The newly established Diabetes Prevention Clinic supports comprehensive care for children with stage 1 and stage 2 T1D, emphasizing surveillance, education, and timely initiation of disease modifying therapy.

(Published January 2026)

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