Transient delayed onset semaglutide-associated rash
Question:
4/1/2024
A 53-year-old woman with type II diabetes had a reaction to Ozempic (Semaglutide).Started on 2.5mg once a day x four weeks and then stepped up to 5.0 mg and after two to three days of being on the higher dose, developed blotchy sl red itchy rash on her chest, abdomen and arms. The rash lasted three days. No other symptoms. She would like to try another GLP1 in particular Mounjaro (Tirzepatide) for weight loss and blood sugar control. What should I recommend? What is the risk of hypersensitivity to other GLP1 therapies? What is the role of skin testing to other agents?
Answer:
The characteristics of the reaction, specifically a diffuse delayed onset benign non-urticarial rash clearing within three days, makes either an IgE-mediated or a severe T-cell mediated event very unlikely. Thus, prick skin testing or patch testing would probably not be helpful.
If semaglutide was otherwise effective, a rechallenge with 5.0 mg and 1 week of observation would be reasonable to determine if semaglutide was responsible for the eruption.
General injection-site reactions including erythema, pain, and rashes have been reported with all of the commercially available GLP-1 receptor agonists. Injection-site nodules have been seen with exenatide extended-release and semaglutide.
Hearn EB, Sherman JJ. Injection-Site Nodules Associated With Once-Weekly Subcutaneous Administration of Semaglutide. Diabetes Spectr. 2021 Jan;34(1):73-75.
At this time there is no good population based data on the risks of immunologically mediated hypersensitivity to more than one glucagon-like peptide 1 receptor agonist.
Semaglutide is a polypeptide that contains a linear sequence of 31 amino acids joined together by peptide linkages, has a molecular weight of 4113 Da, and is over 99% protein bound.
Exenatide is a 39-amino acid peptide amide with a molecular weight of 4187 Da.
Lixisenatide is a 44-amino acid peptide with a single proline substitution and a modified C-terminus of six lysine molecule with a molecular weight of 4858 Da.
Most good protein antigens have molecular weights of more than 8000 Da.
Dulaglutide is a large protein molecule with a molecular weight of 59,669 Da.
Skin testing and patch testing have been done with glucagon-like peptide 1 receptor agonists.
Bianchi L, Ali Biglu Marash S, Malatesta N, Hansel K, Tramontana M, Stingeni L. Hypersensitivity to glucagon-like peptide-1 receptor agonists: a case of delayed urticaria-like rash to dulaglutide and literature review. JEADV Clin Pract. 2024; 3: 313–316. https://doi.org/10.1002/jvc2.255
Eric Macy, MD, MS, FAAAAI