Neuro-Adverse Events Associated with GLP-1 Receptor Agonists: A Study Based on the FAERS Database and External Validation Using NHANES Database

The study examined neurological and psychiatric adverse events of six GLP-1 receptor agonist drugs (semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, and lixisenatide) using FAERS database analysis. Researchers identified 41 significant adverse event signals. Semaglutide showed the strongest neuromuscular signal with muscle atrophy (ROR 3.94), which was also confirmed by tirzepatide (ROR 2.35). Exenatide generated the highest psychiatric signal in the form of nervousness (ROR 4.03). External validation using the NHANES database (17,057 participants, including 70 GLP-1RA users) confirmed higher incidence of depression and reduced sleep hours. The results suggest that these drugs have multiple neurological and psychiatric safety signals, including muscle atrophy as a potential class effect.