GLP-1 RAs May Up Optic Neuropathy Risk in Seniors With Diabetes

TOPLINE:

A Medicare cohort study of nearly 4 million older patients with type 2 diabetes found 2 in 1000 developed nonarteritic anterior ischemic optic neuropathy (NAION) over a period of more than 3 years. The use of GLP-1 receptor agonists (RAs), particularly semaglutide and liraglutide, was associated with an increased risk for the eye condition.

METHODOLOGY:

• Researchers conducted an observational cohort study by analyzing the data of more than 3.8 million Medicare enrollees aged 65 years or older with type 2 diabetes who were prescribed any antidiabetic medication between 2007 and 2021.
• Of those, 15.1% were prescribed GLP-1 agents, 34.8% were prescribed metformin only, 21.7% were prescribed insulin, and the remaining 28.4% were prescribed other comparable second-line antidiabetic medications.
• The association between GLP-1 RAs and the risk for NAION was assessed for the drug class as a whole and for each individual medication (dulaglutide, semaglutide, liraglutide, and exenatide).

TAKEAWAY:

• During a median follow-up duration of 3.7 years, 0.2% of patients (n = 7660) developed NAION.
• The use of any GLP-1 drug was associated with a higher risk for NAION than the use of other second-line antidiabetic medications (hazard ratio [HR], 1.15; 95% CI, 1.04-1.27), with semaglutide showing the highest risk (HR, 1.39; 95% CI, 1.13-1.72), followed by liraglutide (HR, 1.25; 95% CI, 1.08-1.45).
• The use of insulin instead of metformin alone was also linked to an increased risk for NAION in this cohort; other risk factors for NAION were male sex; White race; dual eligibility for Medicare and Medicaid; rural residence; a history of diabetic retinopathy, chronic kidney disease, or obstructive sleep apnea; and the use of antiarrhythmics such as amiodarone.

IN PRACTICE:

“We observed risk variation among the GLP-1 RAs; semaglutide and liraglutide were associated with higher risks,” the researchers reported.

“The risk of NAION warrants further research given the increasing use of GLP-1 RAs and the seriousness of NAION,” they added.

SOURCE:

This study was led by Kin Wah Fung, MD, of the National Institutes of Health in Bethesda, Maryland. It was published online on July 31, 2025, in JAMA Ophthalmology.

LIMITATIONS:

The study’s limitations included reliance on diagnostic codes to identify NAION and lack of information about the onset of diabetes. In addition, the cohort had a narrow age range, limiting the generalizability of the findings.

DISCLOSURES:

This research was supported by the Division of Intramural Research of the National Library of Medicine, National Institutes of Health. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.