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Semaglutide, Tirzepatide Linked to Small Increase in Eye Disorder Risk
There is a low but increased risk of optic nerve disorders in patients with type 2 diabetes prescribed semaglutide or tirzepatide, according to a large cohort study.
Patients with type 2 diabetes (T2D) treated with semaglutide or tirzepatide had a slightly higher risk of developing nonarteritic anterior ischemic optic neuropathy (NAION) and other optic nerve disorders compared with those prescribed other antidiabetic drugs, according to a study.1 While the overall risk remained low, the findings underscore the importance of monitoring for vision-related complications in patients using these medications.
This cohort study is published in JAMA Network Open.
“In our study, we found that patients with type 2 diabetes who were prescribed semaglutide or tirzepatide had various levels of risk of optic nerve and visual pathway disorders, with increased risk of NAION and other optic nerve disorders and no associations with optic neuritis, papilledema, optic atrophy, or optic disc disorders,” wrote the researchers of the study. “Each optic nerve and visual pathway disorder has distinct causes.”
NAION is the most common cause of acute optic nerve injury in adults over age 50.2 It is characterized by sudden, painless vision loss, yet its underlying pathogenesis remains poorly understood, and no proven treatment currently exists. In the US, the annual incidence is estimated at 2.3 to 10.2 per 100,000 among individuals over age 50 and 0.54 per 100,000 across all ages. Men and women are affected equally, and risk is highest among White individuals.
The researchers conducted a cohort study emulating target trials using a nationwide, population-based database of US electronic health records (EHRs) spanning December 2017 to January 2023.1 Eligible participants included more than 1.5 million adults with T2D who had no prior diagnosis of eye disorders and were prescribed either semaglutide, tirzepatide, or other antidiabetic medications.
To reduce confounding, the study used propensity score matching to balance baseline characteristics between groups, resulting in 159,398 matched patients. The primary outcomes were first-time diagnoses of NAION and other optic nerve or visual pathway disorders, assessed over a 2-year follow-up period.
Among the patients with T2D, those prescribed semaglutide or tirzepatide had a higher incidence of optic nerve disorders compared with patients taking other antidiabetic medications. During the follow-up, 35 patients (0.04%) in the semaglutide or tirzepatide group developed NAION, compared with 19 patients (0.02%) in the comparison group (HR, 1.76; 95% CI, 1.01-3.07). Additionally, 93 patients (0.12%) in the treatment group experienced other optic nerve disorders, compared with 54 patients (0.07%) in the control group (HR, 1.65; 95% CI, 1.18-2.31).
No significant associations were observed for other disorders of the optic nerve or visual pathways. Although the absolute risk remained low, the findings suggest a modest but notable increase in risk associated with semaglutide and tirzepatide use.
However, the researchers acknowledged several study limitations, including reliance on retrospective EHR data, which carried risks of unmeasured confounding, bias, and misclassification. Additionally, NAION lacks a specific International Classification of Diseases, Tenth Revision code, which raises potential diagnostic inaccuracies, and medication adherence could not be assessed. The analysis was also limited to patients with T2D in the TriNetX network with 2 years of follow-up, so results may not be generalizable to other populations or longer periods.
Despite these limitations, the researchers believe the study finds a low but increased risk of optic nerve disorders in patients with T2D prescribed semaglutide or tirzepatide.
“Future studies are needed to replicate these findings, explore underlying mechanisms, identify individuals at increased risk for these potential complications, and examine other eye disorders,” wrote the researchers.
References
1. Wang L, Volkow ND, Kaelber DC, et al. 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
2. Wu KY, Evoy F. NAION: Diagnosis and management. American Academy of Ophthalmology. August 1, 2022. Accessed August 18, 2025. https://www.aao.org/eyenet/article/naion-diagnosis-and-management
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