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Ischaemic optic neuropathy (ION) is a rare but vision-threatening complication recently linked to GLP-1 receptor agonists, particularly semaglutide. Using over 30 million reports from the FDA Adverse Event Reporting System (2017–2024), we evaluated formulation- and sex-specific associations. Among 31 774 semaglutide cases, Wegovy demonstrated the strongest signal for ION (reporting odds ratio (ROR)=74.89) compared with Ozempic (ROR=18.81). Sex-stratified analyses showed higher odds in men (ROR=116.37), and multivariable regression confirmed greater risk with Wegovy versus Ozempic (adjusted OR (AOR)=4.74) and in men versus women (AOR=3.33). These findings highlight a potential dose-dependent safety concern that warrants urgent prospective evaluation to guide prescribing and regulatory policy.