Teplizumab has a manageable safety profile in stage 2 and stage 3 type 1 diabetes, meta-analysis suggests
Presenter: Andressa Frankowski Dagostin, MD, San Raffaele University, Milan, Italy
Safety profile of teplizumab in stage 2 and stage 3 type 1 diabetes: a single-arm systematic review and meta-analysis of adverse events. Presented April 23, 2026.
Teplizumab was generally well tolerated across interventional studies in patients with stage 2 and stage 3 type 1 diabetes, according to a systematic review and meta-analysis presented at AACE 2026.
The analysis pooled safety data from 8 studies encompassing 575 participants. Cutaneous, gastrointestinal, cytokine release syndrome-related, and constitutional symptoms were common, but serious adverse events and opportunistic infections were infrequent, according to authors.
Teplizumab, a CD3-directed antibody approved by the FDA in 2022, is indicated to delay the onset of stage 3 type 1 diabetes in at-risk patients with stage 2 disease.
“The pivotal teplizumab trials were designed primarily to test whether teplizumab delays progression or preserves beta-cell function, not to deliver a comprehensive, clinically prioritized safety map across all adverse event categories,” Dr. Dagostin said. “Our meta-analysis addresses that gap by pooling safety data across studies to estimate the frequency and pattern of adverse events.”
The goal of the study, she added, was to translate safety signals into clinical practice, helping clinicians counsel patients, anticipate common toxicities, and identify which adverse events warrant structured monitoring.
Study design
The investigators searched Medline, Embase, Cochrane Central, and clinical trial registries from inception through November 2025. They restricted eligibility to interventional studies of teplizumab in patients with stage 2 or stage 3 type 1 diabetes that included safety data.
Outcomes included treatment discontinuation attributable to adverse events, along with rates of organ-specific events spanning cytokine release syndrome, infections, skin reactions, gastrointestinal complaints, psychiatric symptoms, and hematologic and hepatic abnormalities. Random-effects meta-analyses of proportions were used to pool event rates.
Safety findings
Approximately 9% of patients experienced treatment-emergent adverse events that led to discontinuation, though between-study variability was substantial, authors noted.
Cutaneous adverse events, including rash and pruritus, were the most common category, investigators said. Rash occurred in 60.4% of participants, with a 95% confidence interval of 18.4 to 91.2.
“The wide confidence interval tells us two things: rash is a consistent and clinically relevant safety signal, but its reported incidence varies substantially across studies,” Dr. Dagostin said. “For clinicians, the practical takeaway is to prepare patients for rash and other dermatologic or hypersensitivity-type reactions, but to explain that the expected frequency in a given practice may vary.”
Gastrointestinal symptoms were common but variable, the authors said, with abdominal pain outpacing nausea, vomiting, or diarrhea in frequency of reporting. Cytokine release syndrome occurred in 15.8% of participants.
Headache was reported in 33.3% of participants, fever in 33.3%, and fatigue in 14.8%. Most reported infections were mild and confined to the upper respiratory tract, with no consistent pattern among studies pointing to an elevated risk of opportunistic infection.
Psychiatric signal
Psychiatric disturbances, predominantly mood- and anxiety-related symptoms, were reported in 27.4%.
However, psychiatric findings should not be read as a direct pharmacologic toxicity of teplizumab, Dr. Dagostin said, noting that many participants were children, adolescents, or young adults navigating a recent stage 2 or stage 3 diagnosis in a research setting with frequent monitoring and uncertainty about disease progression.
“It tells clinicians that teplizumab programs should not only monitor labs and infusion reactions; they should also normalize, screen for, and support anxiety and mood symptoms around diagnosis, staging, and treatment,” she said.
Clinical takeaway
If clinicians starting a patient on teplizumab had to prepare for one adverse event category, it would be dermatologic and hypersensitivity-type reactions, especially rash and pruritus, Dr. Dagostin said in an interview.
Rash was the most prominent clinical signal, not only because of its frequency, but because it is highly visible to patients and may influence perceived treatment tolerability, she said.
“In practice, this means preparation should go beyond passive monitoring,” she added. “It requires proactive patient counseling, structured infusion management, and routine laboratory surveillance, including complete blood counts and liver enzymes.”
Disclosures
The authors reported no disclosures related to the study.
References
Dagostin AF, Holland SW, Sa R, et al. Safety profile of teplizumab in stage 2 and stage 3 type 1 diabetes: a single-arm systematic review and meta-analysis of adverse events [abstract]. Endocrine Pract 2026. https://doi.org/10.1016/j.eprac.2026.03.038
Tzield (teplizumab-mzwv) prescribing information. Morristown, N.J.: Provention Bio, Inc; 2026.