Semaglutide Not Associated With Increased Risk of Eye Disorders

A meta-analysis evaluating the relationship between semaglutide and risk of eye disorders has not found any significant association, according to a new study published in JAMA Opthalmology.¹ The authors noted that the relationship between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION) demands further research to confirm any association between them. However, another study, published recently in JAMA Network Open did determine that semaglutide and tirzepatide in patients with type 2 diabetes did lead to an increased risk of NAION.^2,3

Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) that is primarily used in the treatment of diabetes and obesity and has been found to have cardiovascular benefits,⁴ including the reduction of cardiovascular events in those who are overweight or obese. As certain eye disorders can come as an adverse effect related to diabetes, including diabetic retinopathy, the association between semaglutide and the risk of eye disorders is of particular interest in the treatment of both diabetes and eye disorders in conjunction. This meta-analysis aimed to collect data from randomized clinical trials to evaluate the association between ocular adverse effects and semaglutide, specifically as it pertains to the development of NAION and diabetic retinopathy.

Studies from MEDLINE (PubMed), Embase, and Cochrane Central Register were used to perform the meta-analysis. All studies published prior to April 10, 2025, were considered for the analysis. All randomized clinical trials that evaluated adults treated with semaglutide compared with a placebo, no intervention, or an active comparator were included in the analysis. Diabetic retinopathy and NAION were assessed along with any trials reporting adverse events. Studies of any language could be included in the analysis.

There were 78 studies, including 73,640 participants, that were included in the final meta-analysis. A total of 51 reported at least 1 event of eye disorders, 38 reported on diabetic retinopathy, and 5 reported on NAION. There were 52 studies that required diabetes as part of their inclusion criteria. The mean baseline age ranged between 33 and 70 years.

The risk of eye disorders was not changed with the treatment of diabetes using semaglutide. The absolute effect per 1000 study participants was 1 more event when evaluating the studies that included eye disorder adverse effects. The results did not change when studies without eye disorder events were included, and a linear mixed model had consistent results (OR, 1.04; 95% CI, 0.98-1.10). There were no differences based on population (OR, 1.01; 95% CI, 0.91-1.12) or follow-up duration (OR, 1.01; 95% CI, 0.91-1.12). Although semaglutide was shown to be superior to an insulin group, this association was not significant.

There were 38 trials that reported at least 1 event related to diabetic retinopathy, but semaglutide did not affect the risk of diabetic retinopathy. There was an absolute effect of 1 more event per 1000 participants, and this did not change after including trials that did not contain events related to diabetic retinopathy. Consistent results were found in the linear mixed-model analysis (OR, 1.03; 95% CI, 0.96-1.11).

In the 5 trials that reported NAION, semaglutide was associated with a higher risk of NAION (OR, 3.92; 95% CI, 1.02-15.02) with no statistical heterogeneity observed. The trials included 25,330 participants but had a low number of events of NAION, which indicates a need for further study.

There were some limitations to this study. Most of the included studies did not aim to assess ocular adverse events. Ophthalmic assessments were different across the studies, including some studies not including retinal imaging or eye examinations. No diagnostic code was present for NAION in any study. Participants with either proliferative retinopathy or maculopathy were excluded. Some included studies were also not specifically designed to assess NAION even though other ocular adverse events were studied.

The researchers concluded that semaglutide was not associated with an increased risk of eye disorders or diabetic retinopathy.

"We conducted a meta-analysis of randomized clinical trials of semaglutide in diabetes, obesity, and MASLD and did not find a relationship between semaglutide treatment and eye or retinal diseases. However, we found a significant risk of developing NAION with semaglutide," Fernando Gerchman, MD, PhD, and coauthor of the study, said in a statement to The American Journal of Managed Care^®. "Although we confirmed adequacy for diabetic retinopathy, it was not sufficient for NAION, highlighting the need for additional studies to reach definitive conclusions."

References

1. Natividade GR, Spiazzi BF, Baumgarten MW, et al. Ocular adverse events with semaglutide: a systematic review and meta-analysis. JAMA Ophthalmol. Published online August 14, 2025. doi:10.1001/jamaophthalmol.2025.2489

2. Steinzor P. Semaglutide, tirzepatide linked to small increase in eye disorder risk. AJMC^®. August 18, 2025. Accessed August 19, 2025. https://www.ajmc.com/view/semaglutide-tirzepatide-linked-to-small-increase-in-eye-disorder-risk

3. Wang L, Volkow ND, Kaelber DC, Xu R. Semaglutide or tirzepatide and optic nerve and visual pathway disorders in type 2 diabetes. JAMA Netw Open. 2025;8(8):e2526327. doi:10.1001/jamanetworkopen.2025.26327

4. Bonavitacola J. Experts encourage use of GLP-1s in cardiovascular care. AJMC. August 3, 2025. Accessed August 19, 2025. https://www.ajmc.com/view/experts-encourage-use-of-glp-1s-in-cardiovascular-care