Exendin-Based GLP-1 Receptor Agonists Associated With Higher Risk for Anaphylaxis

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Exendin-based GLP-1 receptor agonists have a higher risk for anaphylactic reactions compared with human-analog GLP-1 receptor agonists.

Exendin-based glucagon-like peptide-1 (GLP-1) receptor agonists have double the risk for anaphylactic reactions compared with human-analog GLP-1 receptor agonists, according to pharmacovigilance study results published in The Lancet Diabetes & Endocrinology.

The researchers used VigiBase, the World Health Organization’s individual case safety report database, to perform a pharmacovigilance analysis of exendin-based vs human-analog GLP-1 receptor agonists, given that anaphylactic reactions have been documented with their use. The VigiBase has more than 21 million individual case safety reports from more than 130 countries, reported by healthcare professionals, consumers, and drug manufacturers.

The study included individual case safety reports registered from January 1, 2008 to April 1, 2018 from patients aged ≥18 years who received exendin-based and human-analog GLP-1 receptor agonists. Individual case safety reports that were retrieved using the term “anaphylactic reaction” were considered cases; all other safety reports for the drugs were considered noncases. The researchers performed multivariate logistic regressions using a case-noncase design to determine crude and adjusted reporting odds ratios of anaphylactic reactions.

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Overall, there were 39 cases for human-analog GLP-1 receptor agonists and 24,297 noncases. For exendin-based GLP-1 receptor agonists, there were 98 cases and 43,474 noncases.

Compared with human-analog GLP-1 receptor agonists, the researchers found that exendin-based GLP-1 receptor agonists had an adjusted odds ratio of 2.08 (95% CI, 1.37-3.19). They had consistent results when they restricted their search to physician-reported events, serious events, and exendin-based GLP-1 receptor agonist preparations without metacresol.

The study had several limitations, including potential reporting bias. The researchers also noted that it is unclear whether the association is associated with the active agent or allergenic excipients.

“Given the expected increase in the use of GLP-1 receptor agonists among patients with

type 2 diabetes, particularly among adults with established atherosclerotic cardiovascular disease, our finding…calls for corroboration in large real-world studies,” the researchers wrote.


Pradhan R, Montastruc F, Rousseau V, Patorno E, Azoulay L. Exendin-based glucagon-like peptide-1 receptor agonists and anaphylactic reactions: a pharmacovigilance analysis [published online December 2, 2019]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(19)30382-1