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):712-9. doi: 10.2337/dc23-1911

OBJECTIVE: To assess risk of anaphylaxis among patients with type 2 diabetes mellitus initiating a glucagon-like peptide-1 receptor agonist (GLP-1 RA), with a focus on those initiating lixisenatide.

RESEARCH DESIGN AND METHOD: A cohort study was conducted in 3 large United States claims databases (2017-2021). Adult (aged ≥18 years) new users of a GLP-1 RA with type 2 diabetes mellitus and ≥6 months enrollment in the database before GLP-1 RA initiation (start of follow-up) were included. GLP-1 RAs evaluated were lixisenatide or insulin glargine/lixisenatide fixed-ratio combination (FRC), exenatide, liraglutide or insulin degludec/liraglutide FRC, dulaglutide, and semaglutide (injectable and oral). The first anaphylaxis event during follow-up was identified using a validated algorithm. Incidence rates (IRs) and 95% CIs were calculated within each medication cohort. The unadjusted IR ratio (IRR) comparing anaphylaxis rates in the lixisenatide cohort to all other GLP-1 RAs combined was analyzed post hoc.

RESULTS: There were 696,089 new users with 456,612 person-years of exposure to GLP-1 RAs. Baseline demographics, comorbidities, and use of other prescription medications in the 6 months before index date were similar across medication cohorts. IRs (95% CIs) per 10,000 person-years were 1.0 (0.0-5.6) for lixisenatide, 6.0 (3.6-9.4) for exenatide, 5.1 (3.7-7.0) for liraglutide, 3.9 (3.1-4.8) for dulaglutide, and 3.6 (2.6-4.9) for semaglutide. The IRR (95% CI) for anaphylaxis rate for the lixisenatide cohort compared with the pooled other GLP-1 RA cohort was 0.24 (0.01-1.35).

CONCLUSIONS: Anaphylaxis is rare with GLP-1 RAs. Lixisenatide is unlikely to confer higher risk of anaphylaxis than other GLP-1 RAs.

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