Calculating Glucagon-Like Pepide-1 Receptor Agonist-Associated Medullary Thyroid Cancer Risk: A Novel Integration of the Surveillance, Epidemiology and End Results Cancer Registry and the FDA Adverse Event Reporting System.

Abstract

GLP-1 receptor agonists carry an FDA boxed warning for medullary thyroid carcinoma (MTC) risk, though conflicting clinical evidence has generated tremendous controversy regarding this association. We analyzed SEER and FAERS databases to compare MTC and papillary thyroid cancer (PTC) reporting proportions (RP) between the general population and GLP-1RA users (n = 109 168), controlling for surveillance bias by comparing against other endocrine and non-endocrine drugs. Negative binomial regression was used to estimate the incidence rate ratios (IRR) in the FAERS dataset among patients with reported AEs. The 10-year mean MTC RP in SEER/FAERS was 0.0002%/0.0014%, while PTC was 0.012%/0.0087%. Strikingly, GLP-1RA users showed increased RPs as compared to the total FAERS RPs: MTC 0.071% (50.7-fold increase) and PTC 0.164% (18.9-fold increase) with significantly elevated IRRs (p = 0.0001) compared to reference groups. GLP-1RAs showed a higher RP for MTC compared to other drug classes, warranting prospective studies to investigate further.