Semaglutide Use Linked to Risk for Vision Loss in Diabetes

TOPLINE:

The use of semaglutide in patients with diabetes was associated with a significantly increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) compared with those taking drugs for diabetes that belong to other classes of medication.

METHODOLOGY:

• Researchers conducted a retrospective cohort study (October 2019 – December 2023) utilizing a global electronic health registry to evaluate the risk for NAION among patients with diabetes who were taking semaglutide.
• They included 174,584 patients with diabetes who received semaglutide (mean age, 58.3 years; 51.8% women), propensity matched with an equal number of patients with diabetes who were taking other medications for the condition, such as metformin or sulfonylureas, that are not glucagon-like peptide 1 (GLP-1) receptor agonists.
• The primary outcome was the first diagnosis of NAION following the index date, defined as the date of the first prescription of either semaglutide or another antidiabetic medication.
• Follow-up periods ranged from 1 month to 4 years after the index date.

TAKEAWAY:

• The use of semaglutide was associated with an increased risk for NAION among patients with diabetes throughout the study (hazard ratio [HR], 2.22; 95% CI, 1.37-3.60).
• Semaglutide users showed no significant increase in the risk for NAION during the first year of treatment from the index date.
• The increased risk for NAION in patients with diabetes was associated with the use of semaglutide particularly at the 2-year (HR, 2.39; 95% CI, 1.37-4.18), 3-year (HR, 2.44; 95% CI, 1.44-4.12), and 4-year (HR, 2.05; 95% CI, 1.26-3.34) timepoints from the index date.
• Subgroup analyses indicated a significantly increased risk for NAION associated with the use of semaglutide among women, patients aged 40-64 years, White patients, and patients with concomitant hypertensive diseases compared with the use of the other medications for diabetes.

IN PRACTICE:

“Among patients with diabetes, an elevated risk of NAION was associated with semaglutide use compared with” non–GLP-1 agents, the authors of the study wrote. “Because NAION is a potentially debilitating ophthalmic condition, gaining a clearer understanding of its incidence and the factors influencing its occurrence would enhance care for those considering the use of these medications,” they added.

“Perhaps a more balanced comparison, less subject to indication bias, would be of second-line use of semaglutide with second-line use of a comparable antihyperglycemic medication such as sodium-glucose cotransporter 2 (SGLT2) inhibitors,” according to the authors of an editorial accompanying the journal article.

SOURCE:

This study was led by Alan Y. Hsu, MD, from the China Medical University in Taichung, Taiwan. It was published online on March 27, 2025, in JAMA Ophthalmology.

LIMITATIONS:

The retrospective design of this study prevented establishing direct causality between semaglutide use and NAION development in patients with diabetes. The use of diagnostic codes may have introduced misclassification bias. Additionally, the longitudinal analysis approach may have been subject to potential loss to follow-up and limitations in representativeness.

DISCLOSURES:

No funding information was provided for this study. 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.