Semaglutide use linked to numerically higher retinal vascular event rates in clinical trials

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), like semaglutide, are increasingly prescribed for type 2 diabetes and obesity, demonstrating significant benefits beyond glycemic control. However, the rapid expansion of their use has prompted interest in potential ocular effects. Recent case reports have raised concerns about a possible link between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), highlighting a need to systematically evaluate the risk of retinal vascular events across clinical trials.

This scoping review systematically searched PubMed, Embase, ClinicalTrials.gov, and Google Scholar to identify clinical trials reporting retinal vascular events in patients using semaglutide for type 2 diabetes or obesity. The review included 13 randomized clinical trials, predominantly double-blind and placebo-controlled, comparing 17,478 individuals treated with semaglutide against 17,334 placebo recipients. Reports on optic ischemic neuropathy were also included as a reference outcome to assess the method's capability of detecting rare ophthalmic vascular adverse events.

Across the 13 included randomized clinical trials, a total of 15 retinal vascular events were reported in the semaglutide groups, compared with only 4 events in the placebo arms. In large, long-term trials such as SELECT, SOUL, and FLOW, incidence rates for retinal vascular events remained consistently low but were numerically higher in semaglutide-treated patients. These rates ranged from 0 to 0.33 events per 1,000 person-years in semaglutide groups, versus 0 to 0.05 in placebo groups. In trials utilizing active comparators, rates ranged from 0 to 5.99 events per 1,000 person-years for semaglutide, compared to 0 to 3.52 in comparator groups. For ischemic optic neuropathies, 6 events were reported among 11,757 semaglutide-treated patients versus 1 event among 11,105 placebo-treated individuals. In trials with active comparators, 2 versus 1 event was reported. > Retinal vascular events, particularly retinal arterial occlusions, consistently showed a higher pattern of reporting in the semaglutide arm across the clinical trials reviewed.