Disproportionality analysis on semaglutide and nonarteritic anterior ischemic optic neuropathy in the FDA adverse event reporting system: An emerging pharmacovigilance signal?

Abstract

Background and aim: On January 17th 2025, the European Medicines Agency started a review on semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy (NAION); we gained insight into this potential association by appraising post-marketing reporting.

Methods: We queried the FDA Adverse Event Reporting System (up to December 2024) to retrieve cases of NAION reported with GLP-1 receptor agonists. Disproportionality analysis was performed by calculating the Reporting Odds Ratio (ROR) with 95 % confidence Interval (CI). Signal of Disproportionate Reporting (SDR) was defined by a lower limit of the 95 %CI> 1. To account for potential confounding by indication and channeling bias, active-comparator restricted design and disproportionality by therapeutic area were performed by comparing semaglutide vs other antidiabetic/antiobesity drugs, including SGLT2-inhibitors.

Results: 96 NAION cases were retrieved (83 to semaglutide), peaking 53 in last 3 months (18 from Denmark), with a median time to onset of 186 days. An SDR emerged only for semaglutide (ROR=17.57; 95 %CI=13.93-21.90), and remained significant across comparators and therapeutic indications.

Conclusions: Notwithstanding limitations, including inability to infer causality, the consistency of disproportionality against a wide range of confounders together with other observational evidence raised the hypothesis of a safety signal, especially from Denmark. The exponential reporting trend calls for urgent clarification of drug-, patient- and Country-related risk factors.

Keywords: Disproportionality analysis; FAERS; NAION; Pharmacovigilance; Semaglutide; Signal.