Abstract Details

Title Ischemic Optic Neuropathy With Semaglutide: Global Observational Analysis of Sex- and Formulation-specific Risk

Topic Neuro-ophthalmology/Neuro-otology

Presentation(s) S18 - Neuro-ophthalmology/Neuro-otology (3:30 PM-3:42 PM)

Poster/Presentation
Number 001

Objective

We conducted the first global, population-based observational study of over 30 million reports to compare ischemic optic neuropathy (ION) risk with semaglutide formulations across diabetes and obesity.

Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have transformed cardiometabolic care by improving glycemic control, weight loss, and cardiovascular risk. Recent reports link semaglutide to nonarteritic anterior ischemic optic neuropathy (NAION), with severe vision loss in up to 15% and complete blindness in up to 5%, prompting regulatory action by the European Medicines Agency. No prior study has evaluated formulation- or sex-specific patterns in semaglutide-associated NAION.

Design/Methods We retrieved and deduplicated FDA Adverse Event Reporting System (FAERS) reports from December 2017–December 2024. We included reports naming a GLP-1RA as the primary suspect for ION. Semaglutide was analyzed both as a pooled category and by brand. Comparator drugs were metformin, insulin, and tirzepatide. Disproportionality was assessed using reporting odds ratios (RORs, 95%CIs). Signals met adapted Evans criteria (ROR>2, χ²>4, n≥3), Bonferroni-adjusted significance (p<0.0056; p<0.0028 for sex analyses), and Bayesian confirmation (IC025>0.3). To complement disproportionality estimates, we conducted multivariable logistic regression adjusted for age and sex, generating adjusted odds ratios (AORs, 95%CIs).

Results

Among 30,668,520 FAERS reports, 31,774 involved semaglutide (mean age=56.5±11.1 years; 54.1% female). Wegovy showed the strongest ION signal (n=28, ROR=74.89, 95%CI=51.79–108.29), exceeding Ozempic (n=47, ROR=18.81, 95%CI=14.11–25.07) and pooled semaglutide (n=85, ROR=21.37, 95%CI=17.40–26.65). Other comparators showed no signal: tirzepatide (ROR=0.56), metformin (ROR=1.35), and insulin (ROR=1.61). Sex-stratified analyses showed the highest signal for Wegovy in males (ROR=116.37) and for Ozempic in females (ROR=26.86). In multivariable analysis adjusted for age and sex, odds were higher for Wegovy vs. Ozempic (AOR=4.74, 95%CI=2.54–8.77, p<0.001) and for males vs. females (AOR=3.33, 95%CI=1.89–5.88, p<0.001).

Conclusions Overall, ION risk appears dose- and formulation-dependent, highest with Wegovy. Although Wegovy produced fewer ION reports than Ozempic, its lower overall reporting yielded a higher ROR.

Authors/Disclosures
Moiz Lakhani, BHSc, MD (C) PRESENTER	Mr. Lakhani has nothing to disclose.
Abdullah Al-Ani	Abdullah Al-Ani has nothing to disclose.
Marko Popovic, MD	Dr. Popovic has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Popovic has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche.
Etienne Benard-Seguin, MD	Dr. Benard-Seguin has nothing to disclose.
Edward Margolin, MD	Dr. Margolin has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for J and J.

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