GLP-1 RA drug allergy
Question:
4/10/2024
Do we know anything about allergic reactions to GLP-1 (such as tirzepatide or semaglutide)? If so, is there any cross-reactivity between these two different agonists? Should one expect reactions to semaglutide if a patient had reaction (tongue swelling and chest tightness) after tirzepatide?
Answer:
Cross-reactivity between GLP-1 receptor agonists is unknown. Until these data are available, alternate GLP-1 receptor agonists should be used with caution in patients with a history of anaphylaxis or angioedema other GLP-1 RAs.
In a study by Anthony MS, et al. (1) it was reported that The IR of anaphylaxis in the pooled other GLP-1 RA cohort (including exenatide, liraglutide, dulaglutide, and semaglutide) was 4.2 per 10,000 person-years, compared to versus 1.0 per 10,000 person years in the lixisenatide cohort. The unadjusted IRR for the anaphylaxis rate for the lixisenatide cohort compared with the anaphylaxis rate for the other GLP-1 RA cohort was 0.24.
There are case reports using skin tests in patients with histories of immediate hypersensitivity reactions and delayed hypersensitivity reactions. Starting with 1:000 dilution, 1:100, and 1:10 intradermal. It is recommended that a case control be used since this is not standardized. (2)
If needed, there is a report of seven-step successful desensitization protocol in two cases to exenatide including both local and/or systemic immediate hypersensitivity reactions. (3)
In summary, there may be meaningful difference in risk of anaphylaxis between drugs of this class, with lixisenatide demonstrated to have the lowest risk with IRR 0.24. Though not standardized, a skin test protocol and a desensitization protocol have been published.
1. Anthony MS, Aroda VR, Parlett LE, Djebarri L, Berreghis S, Calingaert B, Beachler DC, Crowe CL, Johannes CB, Juhaeri J, Lanes S, Pan C, Rothman KJ, Saltus CW, Walsh KE. Risk of Anaphylaxis Among New Users of GLP-1 Receptor Agonists: A Cohort Study. Diabetes Care. 2024 Apr 1;47(4):712-719. doi: 10.2337/dc23-1911. PMID: 38363873; PMCID: PMC10973896.
2. Steveling EH, Winzeler B, Bircher AJ. Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. J Pharm Technol. 2014 Oct;30(5):182-186. doi: 10.1177/8755122514539462. Epub 2014 Jun 19. PMID: 34860904; PMCID: PMC5990155.
3. Yeğit OO, Sarıbeyliler G, Karadağ P, Demir S, Gül N, Ünal D, Gelincik Akkor A. The first successful desensitization protocol in exenatide allergy: a case report. Allergy Asthma Clin Immunol. 2023 Jan 13;19(1):2. doi: 10.1186/s13223-023-00761-y. PMID: 36639791; PMCID: PMC9838064.
Respectfully submitted,
Jeffrey G. Demain, MD, FAAAAI