Dose-dependent Risk for Ischemic Optic Neuropathy Found with Semaglutide

Semaglutide, in any formulation, was the only GLP-1 agent significantly associated with ischemic optic neuropathy, with the strongest signal for Wegovy, followed by Ozempic. No ischemic optic neuropathy events were reported for Rybelsus (Novo Nordisk). Other drugs such as tirzepatide, metformin and insulin showed no disproportionality signal. Photo: Novo Nordisk. Click image to enlarge. Recent studies have linked semaglutide, the most commonly prescribed GLP-1 receptor agonist, with increased incidents of the rare but vision-threatening complication of ischemic optic neuropathy. Using 31,774 semaglutide cases from the FDA Adverse Event Reporting System (2017 to 2024), researchers from Canada recently evaluated formulation- and sex-specific associations with patients with diabetes and obesity, with the strongest association observed for the weight-loss formulation of the drug Wegovy (Novo Nordisk).Ozempic generated about seven times more reports than Wegovy, owing to its earlier approval in 2017 vs. Wegovy’s 2021 launch. Despite this difference in volume, Wegovy showed the strongest disproportionality signal for ischemic optic neuropathy (reporting odds ratio [OR]=74.89) compared with Novo Nordisk diabetic drug Ozempic (reporting OR=18.81). Disproportionality reflects relative reporting rather than incidence and may be influenced by exposure, indication or media attention. Sex-stratified analyses showed higher odds in men (reporting OR=116.37), and multivariable regression confirmed greater risk with Wegovy vs. Ozempic (adjusted OR=4.74), as well as in men vs. women (adjusted OR=3.33).Tirzepatide (Mounjaro for diabetes and Zepbound for obesity, both Eli Lilly), a dual GLP-1/GIP agonist titrated gradually across a broad dosing range, showed a favorable safety profile, with GIP agonism probably buffering GLP-1-mediated fluid shifts, stabilizing vascular tone and reducing ischemic vulnerability. “This may further lower non-arteritic anterior ischemic optic neuropathy (NAION) risk indirectly by improving sleep apnea and oxygenation through fat loss,” the researchers commented in their paper.Because this drug showed no disproportionality signal for ischemic optic neuropathy, the study suggests that the risk of NAION may be GLP-1-specific rather than purely metabolic. Although tirzepatide’s shorter availability (about three years vs. over seven years for semaglutide) limits exposure, the reproducible semaglutide signal highlights the need for individualized GLP-1 therapy and prospective risk stratification.Click here for the journal source. Lakhani M, Al-Ani A, Popovic M, et al.  Ischemic optic neuropathy with semaglutide: global observational analysis of sex- and formulation-specific risk. Br J Ophthalmol. March 10, 2026. [Epub ahead of print].  This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.