Ocular adverse events associated with GLP-1 receptor agonists: a Real-World Study Based on the FAERS database and network pharmacology

Objective: This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) by analyzing data from the FDA Adverse Event Reporting System (FAERS) and employing network pharmacology methods.

Methods: FAERS data from the first quarter of 2004 to the first quarter of 2024 were analyzed, focusing on reports of ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis using the Reporting Odds Ratio (ROR) was employed to identify signals of ocular AEs. Additionally, a drug-gene interaction network was constructed using data from multiple public databases to elucidate potential mechanisms underlying these AEs.

Results: Analysis of 17,785,793 reports from the FAERS database revealed significant associations between semaglutide, lixisenatide, and ocular AEs. The ROR for semaglutide was 1.25 (95% CI, 1.20-1.31) and for lixisenatide was 1.96 (95% CI, 1.70-2.27), indicating an increased risk of ocular AEs. Frequently reported ocular AEs included blurred vision, visual impairment, and diabetic retinopathy. Time-to-onset analysis indicated that some AEs could manifest as early as 10 days after treatment initiation. Gene enrichment analysis further highlighted a potential link between GLP-1-related genes and ocular AEs.

Conclusion: The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.