First Reported Case of Skin Reaction at Tirzepatide Injection Site Despite Tolerating Another GLP-1 Drug

A man in his 70s developed an injection site rash on his lower abdomen after switching from dulaglutide (a GLP-1 RA) to tirzepatide (a dual GIP/GLP-1 RA). The rash resolved after stopping tirzepatide. Notably, the patient had tolerated dulaglutide without any injection site reactions, indicating a tirzepatide-specific skin reaction. This was reported as the first documented case of tirzepatide-induced injection site reaction.

This is a single case report documenting the clinical presentation, timeline, and resolution of an injection site reaction after switching from dulaglutide to tirzepatide.

As tirzepatide rapidly gains prescriptions for diabetes and obesity, documenting its adverse effects is important for clinicians. This case shows that patients who tolerate one GLP-1 RA may still develop reactions to tirzepatide, which has a different molecular structure as a dual GIP/GLP-1 receptor agonist. Clinicians should be aware that switching between peptide drugs in this class doesn't guarantee the same tolerability profile.

As tirzepatide prescriptions surge worldwide, post-marketing surveillance of adverse effects becomes increasingly important. This case adds injection site reactions to the known side effect profile of tirzepatide. Since tirzepatide has a unique dual-agonist structure (targeting both GIP and GLP-1 receptors), it may provoke immune responses different from pure GLP-1 agonists, warranting attention as the drug reaches millions of patients.

As a single case report, this represents an isolated observation that cannot establish the frequency or risk factors for tirzepatide injection site reactions. No allergy testing or skin biopsy was described to characterize the nature of the reaction. The mechanism of the tirzepatide-specific reaction was not investigated.