Suspected Biphasic Anaphylaxis Following the First Known Dose of Tirzepatide: A Case Report and Brief Review of Reported Hypersensitivity Reactions

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist increasingly used for type 2 diabetes mellitus and chronic weight management. Although generally well tolerated, serious systemic hypersensitivity reactions may occur. We report a 37-year-old woman who developed anaphylaxis shortly after administering her first known subcutaneous dose of tirzepatide. She presented with facial and periorbital angioedema, nasal congestion, generalized urticaria, bronchospasm, hypoxemia, and hypotension. She was treated with intravenous fluids, nebulized bronchodilators, and two doses of intramuscular epinephrine, resulting in complete clinical resolution. Approximately one hour later, she developed recurrent generalized urticaria, facial angioedema, and chest tightness without further exposure to the suspected trigger. Although no objective respiratory or hemodynamic compromise was documented during the recurrent episode, the recurrence was considered suggestive of a possible biphasic reaction. Her symptoms resolved following treatment with intravenous hydrocortisone and chlorphenamine. Acute and baseline serum tryptase levels were unavailable, and validated allergy testing for tirzepatide was not performed; therefore, the underlying immunological mechanism could not be established. This case highlights the importance of early recognition and prompt treatment of tirzepatide-associated anaphylaxis, as well as continued pharmacovigilance and detailed reporting of severe hypersensitivity reactions.