Purpose: The glucagon-like peptide-1 receptor agonist (GLP-1RA) class of medications are widely prescribed for management of diabetes mellitus as well as obesity or weight management. Although there have been rare reports of skin hypersensitivity associated with GLP-1RA medications, no published reports have documented allodynia or skin pain to the touch.
Summary: We report 4 cases of allodynia associated with dose escalation of the GLP-1RA medication semaglutide. Each patient was prescribed semaglutide for management of obesity and developed symptoms of allodynia with the 2.4-mg subcutaneous once-weekly dose. Therapy was stopped in 2 patients, both of whom had resolution of symptoms. Two patients opted to continue semaglutide despite the adverse effect, with one experiencing resolution after 4 months. No pharmacological mechanism was identified for this unique adverse drug reaction. There was a clear temporal and dose-response relationship in each of the 4 cases.
Conclusion: The 4 cases presented had scores of 5 or 6 (probable) on the Naranjo scale. It is not known whether this is a class effect of the GLP-1RA medications or if the adverse effect will consistently resolve or improve with continuation.
Keywords: adverse drug reaction; allodynia; glucagon-like peptide-1 receptor agonists; semaglutide.
Published by Oxford University Press on behalf of the American Society of Health-System Pharmacists 2025.