A 2025 World Health Organization (WHO) safety alert highlighted concerns regarding a potential association between semaglutide and non-arteritic anterior ischemic optic neuropathy (NAION). Following a review of nonclinical studies, clinical trials, post-marketing surveillance data, and published literature, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) concluded that NAION is a very rare adverse effect of semaglutide, occurring in up to 1 in 10,000 patients. The WHO Advisory Committee on Safety of Medicinal Products subsequently recommended that NAION be included as a potential risk in semaglutide risk management plans. The WHO advised that patients experiencing sudden vision loss or rapidly worsening vision during semaglutide therapy should undergo prompt evaluation and that semaglutide should be discontinued if NAION is confirmed. This recommendation was based on pharmacovigilance and safety review data rather than studies evaluating outcomes after continuation versus discontinuation of semaglutide following a NAION diagnosis. [1]
A 2026 systematic review evaluated nine retrospective cohort studies involving more than 3 million patients and found conflicting evidence regarding an association between semaglutide and NAION. Four studies reported an increased risk of NAION, with hazard ratios ranging from 1.76 to 4.28, while four studies found no significant association and one study reported a protective effect. The authors noted that studies demonstrating increased risk generally used broad comparator groups, whereas studies using active comparators with similar metabolic risk profiles consistently found no association. The review concluded that current evidence does not support a causal relationship between semaglutide and NAION and that the conflicting findings are most likely explained by confounding by indication, as patients prescribed semaglutide often have more severe diabetes, obesity, and cardiovascular disease, which are independent risk factors for NAION. Even under the highest reported risk estimates, the absolute risk remained very low and was substantially outweighed by the established cardiovascular and renal benefits of semaglutide. The authors also stated that current evidence does not support routine NAION screening or treatment discontinuation in asymptomatic patients and emphasized that clinicians should counsel patients regarding the overall favorable benefit-risk profile of semaglutide while remaining vigilant for rare adverse events. Of note, the review did not discuss whether semaglutide should be discontinued in patients who develop symptomatic or confirmed NAION, nor did it evaluate outcomes after continuation versus discontinuation of therapy. [2]
Another systematic review, published in 2025, similarly evaluated nine studies examining the potential association between semaglutide and NAION. Findings were inconsistent, with several cohort and pharmacovigilance studies reporting a modest increase in NAION risk, while other matched cohort and real-world studies found no significant association after adjustment for confounding factors. Heterogeneity in study design, patient populations, exposure definitions, outcome ascertainment, and diagnostic criteria limited comparability across studies and precluded meta-analysis. Proposed mechanisms remain speculative, although vascular effects on optic nerve perfusion and rapid glycemic improvement have been suggested. Overall, the authors concluded that the absolute risk of NAION appears to be low and that semaglutide's established metabolic and cardiovascular benefits likely outweigh potential ocular risks for most patients. Current evidence does not support widespread changes to clinical practice; however, clinicians should exercise caution in patients with predisposing ocular anatomy, such as crowded optic nerve heads, small Bruch's membrane opening, or optic disc drusen, and additional prospective ophthalmology-focused studies are needed to clarify whether a causal relationship exists. [3]