Cutaneous Allodynia Associated With GLP-1RA Tirzepatide for Weight Management: A Case Series

BACKGROUND Cutaneous allodynia is reported as a pain resulting from a stimulus that does not normally provoke or elicit pain and an altered quality of sensation characterized by extreme sensitivity to touch or mild temperature change. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for management of diabetes mellitus and for obesity and weight management. Tirzepatide is a synthetic polypeptide and dual agonist for glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide receptors. Clinical studies demonstrate that tirzepatide provides robust glycemic control and is highly effective for the treatment of obesity. Review of the tirzepatide U.S. prescribing information revealed hypersensitivity and injection site reactions as the only dermatological adverse events, with no reports of skin pain or allodynia. A recent pharmacovigilance analysis of the U.S. Food and Drug Administration Adverse Event Reporting System evaluating 6 GLP-1RAs, including tirzepatide, identified rare reports of allodynia; however, detailed case-level descriptions remain limited. CASE REPORT In this case series, we report moderate-to-severe allodynia in 2 patients with severe obesity treated with tirzepatide for weight management. Allodynia in these patients varied from static to dynamic in nature; the incidence of allodynia was temporally associated with dose escalation, related to higher doses, and resolved after termination of the drug, demonstrating strong association with tirzepatide treatment. CONCLUSIONS Although dermatologic adverse events, such as injection site reactions, hypersensitivity, and urticaria, have been reported, to the best of our knowledge, this is the first case series reporting allodynia specifically with tirzepatide therapy.