Semaglutide Linked to Increased Risk of Rare, Debilitating Eye Condition

Patients with type 2 diabetes treated with semaglutide (Ozempic) face an increased risk of developing a rare but serious eye condition, nonarteritic anterior ischemic optic neuropathy (NAION), according to a pair of studies from the University of Southern Denmark (SDU).¹

NAION is a rare but serious eye condition caused by reduced blood flow to the optic nerve.² It typically leads to sudden vision loss, particularly in sharpness and field of vision. Risk factors for NAION include diabetes, high blood pressure, high cholesterol, and specific anatomical conditions of the eye.

These new findings validate earlier concerns raised in an American study, which initially linked semaglutide use with NAION risk.³ In the 2 separate studies, researchers Jakob Grauslund, MD, PhD, professor of ophthalmology, and Anton Pottegård, PhD, professor of pharmaceuticals, analyzed health data from Denmark and Norway using different methods and reached the same conclusion: the risk of NAION more than doubles for patients taking semaglutide.¹

Ozempic was linked to a doubled risk of NAION for patients with diabetes | Image credit: mbruxelle – stock.adobe.com

In Grauslund’s study, researchers examined a nationwide cohort of 424,152 Danes with type 2 diabetes, 106,454 of whom were treated with semaglutide. The study found that patients taking the glucagon-like peptide 1 (GLP-1) receptor agonists had a 2.19 times higher risk of developing NAION compared with those receiving other diabetes treatments.

Notably, Denmark saw its annual average of first-time NAION cases rise from 67.6 to 148 cases since Ozempic’s introduction in 2018. At the same time, the rate of diabetes in newly-diagnosed NAION jumped from 1 in 20 cases to 1 in 4.

“Fortunately, according to our study the number of people affected is lower than was found in the American study, but the number of cases of NAION among the people who are receiving Ozempic has still doubled,” Grauslund said in the news release.

Meanwhile, Pottegård’s team compared new semaglutide users with those starting alternative treatments and found an even greater risk: patients taking semaglutide had a 2.81 times higher relative risk of NAION. However, the absolute risk increase was limited, with as little as 1.4 to 2.5 excess NAION events per 10,000 years of follow-up among semaglutide users. This study is still undergoing peer review.

“Although our findings thereby do not rule out the possibility of an increased risk of NAION when using semaglutide for obesity, the low number of observed events suggests that any potential risk is likely of limited absolute magnitude,” Pottegård’s research team said.⁴ “Additional analyses with appropriate comparators or other study designs are needed to further investigate whether an increased risk of NAION is also evident among users of semaglutide for obesity and if so, the magnitude of this risk.”

Reassessing Diabetes Treatment Plans

While these findings are important, they do not mean all patients should discontinue the GLP-1 receptor agonist. Kurt Højlund, MD, PhD, professor of diabetes at SDU and Odense University Hospital, noted that the drug remains a crucial treatment option for type 2 diabetes, but patients and doctors should carefully weigh the risks and benefits.¹

“It is extremely important that type 2 diabetes is treated, but you have to consider whether the small increased risk of severe vision loss by using Ozempic means that you should instead use one of the other new drugs that protect against kidney and cardiovascular disease,” he said in the news release.

Aside from risk factors, there is no way to identify with certainty who is at a particularly high risk of NAION. However, Højlund advised that doctors stop treatment with semaglutide once NAION is detected.

“The vast majority of patients can be confident in receiving treatment with Ozempic, as the absolute risk is so low, but some people may prefer an alternative treatment following consultation with their doctor,” Højlund added.

These findings have been shared with Danish and international health authorities, who are actively investigating NAION as a potential side effect of semaglutide. While this research focused on Ozempic, Pottegård noted that cases of NAION have also been observed with Wegovy, a higher-dose version of semaglutide used for weight loss. Early data suggest that the risk with Wegovy may be lower, though more research is needed.

References

1. Danish diabetes medicine increases the risk of severely debilitating eye condition. News release. University of Southern Denmark. December 16, 2024. Accessed December 16, 2024. https://www.sdu.dk/en/om-sdu/fakulteterne/sundhedsvidenskab/nyheder/dansk-diabetesmedicin-oger-risikoen-for-svaert-invaliderende-ojensygdom
2. Non-arteritic anterior ischemic optic neuropathy (NAION). Brigham and Women’s Hospital. Accessed December 16, 2024. https://www.brighamandwomens.org/neurology/neuro-ophthalmology/non-arteritic-anterior-ischemic-optic-neuropathy
3. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol. 2024;142(8):732-739. doi:10.1001/jamaophthalmol.2024.2296
4. Simonsen E, Lund LC, Ernst MT, et al. Use of semaglutide and risk of non-arteritic anterior ischemic optic neuropathy: a Danish–Norwegian cohort study. medRxiv. Published online December 11. 2024. doi:10.1101/2024.12.09.24318574