The risk of retinal vascular events in patients using semaglutide: a scoping review

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Abstract
Background This scoping review aims to explore existing clinical trials on the association between semaglutide use and the occurrence of retinal vascular events to detect any potential safety concern. Summary The review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Reviews guidelines. A search was performed across PubMed, Embase via Ovid, ClinicalTrials.gov, and Google Scholar on April 16th, 2025, and Marts 5th, 2026. We aimed to detect clinical trials reporting retinal vascular events while investigating the effect of semaglutide in patients with type 2 diabetes or obesity. Reports on optic ischemic neuropathy were included as a reference outcome, to evaluate whether the method used in the review might be capable of detecting rare ophthalmic vascular adverse events, and thereby a potential safety signal. Key Messages Thirteen randomized clinical trials (predominantly double-blind and placebo-controlled) were included, comparing 17,478 individuals treated with semaglutide and 17,334 placebos. A total of 15 retinal vascular events were reported in the semaglutide groups compared with four events in placebo arms. In large, long-term trials (SELECT, SOUL, FLOW), incidence rates were consistently low but numerically higher in semaglutide-treated patients, ranging from 0 to 0.33 events per 1,000 person-years versus 0 to 0.05 in placebo groups. In trials with active comparators, rates ranged from 0 to 5.99 events per 1,000 person-years in semaglutide groups and 0 to 3.52 in comparator groups. For ischemic optic neuropathies, six events were reported among 11,757 semaglutide-treated patients versus one event among 11,105 placebo-treated individuals; in trials with active comparators, two versus one event were reported. In conclusion, retinal vascular events, especially retinal arterial occlusions, showed a higher pattern of reporting in the semaglutide arm across clinical trials, the majority of which were randomized placebo-controlled-trials. Optic ischemic neuropathies were also found to be higher on the semaglutide-arm. These findings support the need for further investigation through large-scale registry studies.

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