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On July 3, 2024, researchers from the Harvard T.H. Chan School of Public Health and Massachusetts Eye and Ear, Harvard Medical School published a research paper titled "Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide" in JAMA Ophthalmology, a subsidiary journal of JAMA.

The study found that patients using semaglutide for diabetes or weight loss had a higher risk of developing Nonarteritic Anterior Ischemic Optic Neuropathy (NAION), a potentially blinding eye condition, compared to similar patients not using semaglutide. Specifically, those using semaglutide for type 2 diabetes were over 4 times more likely to be diagnosed with NAION, while those using it for weight loss were over 7 times more likely.

▍Professor Joseph Rizzo, the corresponding author of the paper, stated that the use of semaglutide has been growing explosively. While these drugs provide significant benefits in many aspects, future discussions between patients and doctors should include the potential risk of NAION.

NAION is a relatively rare condition, affecting approximately 10 in 100,000 people in the general population. It is the second leading cause of optic nerve blindness (second only to glaucoma) and the most common cause of sudden optic nerve blindness.

NAION is believed to be caused by reduced blood flow to the anterior portion of the optic nerve, resulting in permanent vision loss in one eye. The vision loss caused by NAION is painless, may persist for several days before stabilizing, and has a relatively small chance of improvement. Currently, there is no effective treatment for NAION.

This research began in late summer 2023 when the research team noticed a concerning trend in their clinical practice - three patients were diagnosed with vision loss due to this relatively rare optic nerve condition in just one week, and all three were using semaglutide.

This coincidental discovery prompted the research team to conduct a retrospective analysis of previous patients to determine if this optic nerve condition was related to the increasingly popular semaglutide.

The research team analyzed over 16,827 patients at Massachusetts Eye and Ear, Harvard Medical School since semaglutide was approved for treating type 2 diabetes in 2017. They divided these patients into diabetes and overweight/obese groups. The team then compared patients receiving semaglutide treatment with those using other diabetes medications or weight loss drugs, analyzing the diagnosis rates of NAION in each group.

Specifically, among the 16,827 patients, 710 had type 2 diabetes (194 using semaglutide; 516 using non-GLP-1 receptor agonist antidiabetic drugs), and 979 were overweight or obese (361 using semaglutide; 618 using non-GLP-1 receptor agonist weight loss drugs).

● In the type 2 diabetes patient group, there were 17 NAION events among patients using semaglutide, compared to only 6 in the non-GLP-1 receptor agonist queue. Within 36 months, the cumulative incidence rates of NAION in the semaglutide and non-GLP-1 receptor agonist queues were 8.9% and 1.8%, respectively. The Cox proportional hazards regression model showed that patients receiving semaglutide treatment had a higher risk of NAION (hazard ratio of 4.28).

● In the overweight or obese patient group, there were 20 NAION events in the semaglutide queue, compared to only 3 in the non-GLP-1 receptor agonist queue. Within 36 months, the cumulative incidence rates of NAION in the semaglutide and non-GLP-1 receptor agonist queues were 6.7% and 0.8%, respectively. The Cox proportional hazards regression model showed that patients using semaglutide had a higher risk of NAION (hazard ratio of 7.64).

These results indicate an association between semaglutide and NAION. It's important to note that this study did not prove a causal relationship between semaglutide use and NAION. The research team is also unclear about why this association exists and why there are differences in NAION incidence rates between the diabetes and overweight/obese groups. Therefore, further research is needed in larger, more diverse populations.

Reference

Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. Published online July 03, 2024. doi:10.1001/jamaophthalmol.2024.2296