Thyroid Hyperplasia and Neoplasm Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists in the Food and Drug Administration Adverse Event Reporting System: Retrospective Analysis.

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are one of the most commonly used drugs for type 2 diabetes mellitus. Clinical guidelines recommend GLP-1 RAs as an adjunct to diabetes therapy in patients with chronic kidney disease, presence or risk of atherosclerotic cardiovascular disease, and obesity. The weight loss observed in clinical trials has been explored further in healthy individuals, putting GLP-1 RAs on track to be the next weight loss treatment.

Objective: Although the adverse event profile is relatively safe, most GLP-1 RAs come with a labeled boxed warning for the risk of thyroid cancers, based on animal models and some postmarketing case reports in humans. Considering the increasing popularity of this drug class and its expansion into a new popular indication, a further review of the most recent postmarketing safety data was warranted to quantify thyroid hyperplasia and neoplasm instances.

Methods: GLP-1 RA patient reports from the US Food and Drug Administration (FDA) Adverse Event Reporting System database were analyzed using reporting odds ratios and 95% CIs.

Results: In this study, we analyzed over 18 million reports from the US FDA Adverse Event Reporting System and provided evidence of significantly increased propensity for thyroid hyperplasias and neoplasms in patients taking GLP-1 RA monotherapy when compared to patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitor monotherapy.

Conclusions: GLP-1 RAs, regardless of indication, are associated with an over 10-fold increase in thyroid neoplasm and hyperplasia adverse event reporting when compared to SGLT-2 inhibitors.