Elnaz Khani, Hila Asham, Aysa Rezabakhsh, Shima Babaei, Taher Entezari-Maleki
Despite the recent reports of the potential association between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), available evidence remains inconclusive. We aimed to evaluate the relative effect (RE) of NAION in individuals treated with semaglutide compared to the control group. The results of this systematic review and meta-analysis were reported according to the PRISMA guidelines. The study protocol was prospectively registered in PROSPERO with ID: CRD42025649542. A systematic search was performed on the PubMed, Embase, and Cochrane Library databases until May 18, 2026. Meta-analysis of REs with 95% confidence intervals (CI) was calculated using random-effects models. Eight observational cohort studies, involving a total of 5,916,559 participants, were included in the meta-analysis. Of these, 1,870,346 patients received semaglutide treatment, while 4,046,213 were administered non-semaglutide treatment. Compared to non-semaglutide-treated patients, semaglutide users had a higher risk of NAION (RE, 1.93; 95% CI, 1.22-3.08; I2, 91%; P = .01). There was a significant association between NAION risk and semaglutide use in individuals with diabetes (RE, 1.84; 95% CI, 1.21-2.80; I2, 88.26%; P < .01). However, the results were non-significant among overweight or obese individuals (RE, 1.68; 95% CI, 0.72-3.91; I2, 83.98%; P = .23). The current meta-analysis suggests a possible association between semaglutide and risk of NAION. Further randomized clinical trials are required to draw a clear conclusion.