IMPORTANCE: Semaglutide is a widely used treatment for diabetes and obesity, offering considerable cardiovascular benefit. However, its association with ocular adverse events remains uncertain.
OBJECTIVE: To assess the incidence of eye disorders, diabetic retinopathy, and nonarteritic anterior ischemic optic neuropathy (NAION) in adults treated with semaglutide.
DATA SOURCES: A comprehensive electronic search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials was conducted on April 10, 2025, without date restrictions.
STUDY SELECTION: Investigators independently screened records to identify randomized clinical trials comparing semaglutide with either an active comparator or placebo in adults, assessing ocular adverse events.
DATA EXTRACTION AND SYNTHESIS: Descriptive synthesis of the included studies was performed. The random-effects model using the inverse variance method was used to summarize the odds ratio (OR) for eye disorders and diabetic retinopathy. Peto OR with a fixed-effects model was applied for NAION. Risk of bias was assessed with the RoB 2.0 tool and quality of evidence with GRADE. Trial sequential analysis (TSA) was performed to determine whether the available data were sufficient for definitive conclusions.
MAIN OUTCOMES AND MEASURES: The primary outcomes included the number of patients experiencing an ocular adverse event, diabetic retinopathy, or NAION. Subgroup analyses were conducted based on follow-up duration, comparator type, and primary baseline condition.
RESULTS: A total of 78 trials with 73 640 participants were included. Semaglutide did not increase or reduce the risk of eye disorders (OR, 1.01; 95% CI, 0.91-1.12) or diabetic retinopathy (OR, 1.04; 95% CI, 0.92-1.17). Treatment with semaglutide was associated with a significant odds of NAION (OR, 3.92; 95% CI, 1.02-15.02). Overall risk of bias was low. TSA provided evidence that the sample size was sufficient to avoid missing alternative results for diabetic retinopathy but not for NAION.
CONCLUSIONS AND RELEVANCE: These findings suggest that semaglutide was not associated with an increased risk of eye disorders or diabetic retinopathy. Despite the fact that an association between semaglutide treatment and NAION was found, current evidence remains insufficient to establish definitive conclusions regarding its association with NAION. Further studies with larger sample sizes and adequate evaluation of NAION are warranted to clarify this potential risk.