Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide

To report a case of systemic hypersensitivity to the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide used in diabetes care to provide significant information within the context of postmarketing safety surveillance of this new drug class. We report on a 52-year-old male with insufficiently controlled diabetes. GLP-1 agonist treatment was indicated and the patient was started on 5 to 10 µg exenatide (Byetta) twice daily, which had to be stopped after 1 month due to intolerable nausea. One year later, an attempt with 0.6 to 1.8 mg liraglutide (Victoza) once daily was well tolerated but lacked efficacy after a few months. Finally, the patient was started on 2 mg exenatide (Bydureon) once weekly. Concomitant treatment included metformine 1000 mg twice daily and candesartan/hydrochlorothiazide (Blopress Plus) 16/12.5 mg once daily. A few hours after the second injection, local urticaria and disseminated pruritus evolved and after the third injection pruritus, urticaria, and shortness of breath developed, which resolved to antihistamines and corticosteroids. Intradermal tests were positive for Byetta (1:1000) and Bydureon (1:100) (both exenatide), while Victoza (liraglutide) was negative (1:10). Specific immunoglobulin E (IgE) to the drugs was not available for testing. An objective causality assessment revealed that the adverse effect to exenatide (Bydureon) was probable (Naranjo probability scale: score of 8). Consistency was established through positive skin tests and the biological explanation that the administration of GLP-1 receptor agonists has been associated with antibody formation. Considering emerging use of GLP-1 receptor agonists, systemic hypersensitivity should be recognized as a risk in clinical practice.