Psychiatric and eye disorders associated with use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs)

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) semaglutide, liraglutide, and dulaglutide are indicated for diabetes. Semaglutide and liraglutide were also approved for therapy of obesity or weight control. Apprehension has been expressed about the possible link between GLP-1 RAs and suicidality. Drug agencies established no causal relationship, but declaring that this risk cannot be underevaluated. We analyzed spontaneous signals of suspected adverse reactions (SARs) to liraglutide, semaglutide, and dulaglutide from EudraVigilance database for the years 2020-2025, to give a contribution in the definition of safety profile of GLP-1 RAs. SARs to semaglutide, liraglutide, and dulaglutide were analyzed, and descriptive and disproportionality analysis for adverse reactions was performed. Eye disorders were more frequently reported with semaglutide than liraglutide (ROR 2.67; 95% CI 1.54-4.63) and dulaglutide (ROR 1.89; 95% CI 1.30-2.75). Suicidal ideation was disproportionately reported with semaglutide (ROR 6.49; 95% CI 1.57-26.81) and liraglutide (ROR 8.61; 95% CI 1.87-39.45) compared with dulaglutide. Data suggest the need of further research and vigilance on the potential occurrence of eye disorders related to GLP-1 RAs semaglutide and liraglutide use and suggest not to underestimate the possibility of a link between these two drugs and suicidality. Caution is suggested when GLP-1 RAs are prescribed for patients characterized by ophthalmic and neuropsychiatric vulnerability.