Rapid oral desensitization to semaglutide following anaphylaxis with positive intradermal testing

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for the treatment of type 2 diabetes mellitus (T2DM) and obesity due to their glycemic and metabolic benefits. Although hypersensitivity reactions have been described, anaphylaxis to oral semaglutide remains rare.3 To date, no standardized desensitization protocol for oral semaglutide has been established. Case report: A 60-year-old woman developed immediate anaphylaxis within minutes of ingesting oral semaglutide (3 mg/day). Symptoms included generalized urticaria, facial angioedema, laryngospasm, and dyspnea, requiring intramuscular epinephrine. Serum tryptase was not obtained due to resource limitations. Skin testing was performed using concentrations previously reported as nonirritating. Intradermal testing was positive at 1:10 dilution, supporting an IgE-mediated mechanism. Due to significant metabolic benefit and lack of effective alternatives, a rapid 13-step oral desensitization protocol was performed with premedication. The patient has remained asymptomatic under continuous daily therapy since September 2025. Conclusions: Rapid oral desensitization may allow safe continuation of semaglutide in selected patients with confirmed immediate hypersensitivity when no suitable alternatives exist.