CureusSep 4, 2026

Possible Two-Phase Allergic Reaction After First Dose of Tirzepatide: A Case Report and Summary of Similar Reactions

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 5, 2026

Abstract

A 37-year-old woman experienced anaphylaxis after her first dose of tirzepatide.

Symptoms included facial and periorbital swelling, nasal congestion, widespread hives, difficulty breathing, low oxygen levels, and low blood pressure.
Initial treatment with intravenous fluids and epinephrine led to complete resolution of symptoms.
Recurrent symptoms occurred about one hour later without additional exposure to tirzepatide, suggesting a potential biphasic reaction.
No objective respiratory or blood pressure problems were documented during the second episode.
Treatment for the recurrent symptoms included intravenous hydrocortisone and chlorphenamine.
The absence of serum tryptase levels and allergy testing limited the understanding of the immunological mechanism.

Simplified

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.

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Possible Two-Phase Allergic Reaction After First Dose of Tirzepatide: A Case Report and Summary of Similar Reactions

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