Does semaglutide use raise NAION risk?

Users of semaglutide do not appear to be at greater risk of developing nonarteritic anterior ischaemic optic neuropathy (NAION), suggests a study.

A team of investigators did a thorough search of Medline, Embase, Central, clinical trial registries, and direct contact with trial sponsors to identify unpublished data from inception to March 2025. Observational studies and randomized controlled trials (RCTs) evaluating semaglutide vs placebo or standard therapy in adults were included. The primary outcome was incident NAION.

Random-effects models, stratified by both clinical indication (diabetes/weight loss) and study design, were used to calculate pooled incidence rates, hazard ratios (HRs), and risk ratios (RRs) with 95 percent confidence intervals (CIs).

Eight RCTs (31,174 patients, including three RCTs not previously synthesized in meta-analyses) and eight observational studies (1,611,278 patients) met the eligibility criteria.

Observational studies for diabetes reported a pooled NAION incidence of 26.7 per 100,000 person-years among semaglutide users compared with 18.9 per 100,000 person-years among nonusers (HR, 1.85, 95 percent CI, 1.20‒2.85).

In RCTs for diabetes, five ischaemic optic neuropathy events were found in semaglutide users compared with one in nonusers, with no significant evidence of increased risk (RR, 1.76, 95 percent CI, 0.43‒7.25).

Observational studies of semaglutide for weight loss found no evidence of increased NAION risks (HR, 1.57, 95 percent CI, 0.69‒3.59), as did the RCTs (4 ION events vs 1; RR, 2.18, 95 percent CI, 0.33‒14.34).

“The comprehensiveness of our search and rigorous sensitivity analyses to account for patient overlap in databases strengthen the validity of these conclusions,” the investigators said. “This synthesis highlights the need for continued pharmacovigilance while contextualizing the low absolute risk.”