Neuro-Adverse Events Associated with GLP-1 Receptor Agonists: A Study Based on the FAERS Database and External Validation Using NHANES Database
GLP-1 receptor agonists, including semaglutide, are associated with significant neuropsychiatric safety signals, warranting careful monitoring in clinical practice.
Where it sits
this study against the rest of the semaglutide corpusSummary and findings
This study evaluated neuro-adverse events associated with GLP-1 receptor agonists, including semaglutide, using FAERS and NHANES databases. The analysis identified significant neuro-adverse event signals, particularly highlighting muscle atrophy for semaglutide. The study also reported increased depression odds and reduced sleep hours among GLP-1RA users.
Abstract
<h4>Background: </h4> Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely prescribed for type 2 diabetes and obesity, yet their neuropsychiatric safety profile remains incompletely characterized. We aimed to systematically evaluate neuro-adverse event (AE) signals for six GLP-1RAs and to validate key findings using population-based data. Methods We conducted disproportionality analysis of FAERS data for semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, and lixisenatide. RORs were calculated for 93 predefined neuro-AE MedDRA PTs across 11 neurological categories. External validation used NHANES 2013-2018 (n=17,057; 70 GLP-1RA users) with survey-weighted regression. Results We identified 41 significant neuro-AE signals. Semaglutide showed the strongest neuromuscular signal, muscle atrophy (ROR 3.94; 95%CI 3.42-4.54), corroborated by tirzepatide (ROR 2.35; 95%CI 2.04-2.71). Exenatide generated the highest psychiatric signal: nervousness (ROR 4.03; 95%CI 3.70-4.40). NHANES confirmed higher depression odds (OR 2.05; 95%CI 1.32-3.19; P=0.001) and reduced sleep hours (beta -0.35; P=0.033). Conclusions GLP-1RAs carry multiple neuropsychiatric safety signals, including muscle atrophy as a potential class effect and depression risk corroborated by population-level data. These findings support heightened clinical monitoring.