Pharmacovigilance analysis of neurological adverse events associated with GLP-1 receptor agonists based on the FDA Adverse Event Reporting System

We performed a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) database (2005 Q2–2024 Q3) to investigate neurological adverse events (NAEs) associated with six glucagon-like peptide-1 receptor agonists (GLP-1 RAs): exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, and tirzepatide. Among 28,953 NAE reports linked to GLP-1 RAs, 19 distinct signals were identified using reporting odds ratios (RORs), including dizziness, tremor, dysgeusia, lethargy, taste disorder, presyncope, parosmia, allodynia, and hypoglycemic unconsciousness. Time-to-onset analysis showed a median latency of 32 days (IQR 7–122), with 45.3% of cases occurring within 30 days of treatment initiation. Sensitivity analyses using proportional reporting ratios (PRRs), information components (ICs), and empirical Bayes geometric means (EBGMs) confirmed the robustness of these signals. While these pharmacovigilance findings highlight the need for increased clinical awareness, they reflect associations rather than causality, given the inherent limitations of FAERS, including reporting bias and confounding. Prospective studies are warranted to validate these associations and elucidate underlying mechanisms.