Researchers Identify Potential Link Between Semaglutide and Nonarthritic Anterior Ischemic Optic Neuropathy

Patients who receive GLP-1 receptor agonist semaglutide (Ozempic; Novo Nordisk) may have an increased risk of developing nonarthritic anterior ischemic optic neuropathy (NAION), according to a study published by researchers from Havard Medical School in Boston. The preliminary observational data collected emphasize the need to further investigate instances of NAION in patients treated with semaglutide to identify the causal relationship between GLP-1 hormones and eye health.

Semaglutide are widely used to manage type 2 diabetes (T2D) by increasing insulin levels in the body to decrease blood glucose levels through GLP-1, a hormone that indicates fullness and regulates insulin levels. Quick or sudden fluctuations in glucose levels can affect the shape of the eye lens, often resulting in blurred vision. Additionally, high levels of prolonged glucose circulation in the bloodstream may lead to damage of the blood vessels and nerves in the eyes, which can cause diabetic retinopathy.^1-3

Following a 3-year mean follow-up, researchers found that patients with diabetes on semaglutide had a 4-fold higher risk of developing NAION, a condition characterized by the impaired blood circulation to the optic nerve. The underlying mechanism causing NAION is unknown; however, several risk factors, such as diabetes, high blood pressure, and sleep apnea, may increase the risk in affected individuals. In the study, the authors aimed to identify the potential association between development of NAION and use of semaglutide.^1-3

In a retrospective matched cohort study used, data were collected from a centralized registry of patients evaluated by neuro-opthalmologists between December 1, 2017, and November 30, 2023. Researchers used propensity matching to determine whether semaglutide treatments were associated with NAION in patients with T2D or in those who are overweight or obese, accounting for various factors including sex, age, presence of cardiovascular diseases, and any contraindications for using semaglutide.⁴

Using the Kaplan Meier method and Cox proportional hazards regression model, they assessed the cumulative incidence of NAION in a population of 16,827 patients with either T2D (n=710; 194 prescribed semaglutide; 516 prescribed non–GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) or who were overweight or obese (n=979; 361 prescribed semaglutide; 618 prescribed non–GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female).⁴

In the T2D cohort, the researchers observed 17 NAION events among patients prescribed semaglutide compared with 6 events in patients receiving non-GLP-1 RA antidiabetic medications. The cumulative incidence over 36 months was 8.9% for the semaglutide cohort (95% CI, 4.5%-13.1%) vs 1.8% in the non-GLP-1 RA cohort (95% CI, 0%-3.5%). The cox proportional hazards regression model indicated a higher risk of NAION for patients receiving semaglutide (hazard ratio [HR] of 4.28 [95% CI, 1.62-11.29; P 4

In the cohort of patients who were overweight or obese, there were 20 NAION events in those receiving semaglutide treatment vs 3 in the non-GLP-1 RA cohort. Over 36 months, the cumulative incidence of NAION was 6.7% in the semaglutide cohort (95% CI, 3.6%-9.7%) compared with 0.8% in the non-GLP-1 RA cohort (95% CI, 0%-1.8%). The researchers reported a HR of 7.64 (95% CI, 2.21-26.36; P 4

The findings demonstrate potential associations between NAION and semaglutide use in both cohorts; additionally, the findings suggest that patients with diabetes have a higher risk of developing NAION compared with patients who are overweight or obese. However, due to the study’s observational design, further investigations are needed to assess causality and confirm the link between semaglutide and NAION.⁴

The American Academy of Ophthalmology recommends patients continue their prescribed use of semaglutide and refer to their care teams to determine needed treatment adjustments. Additionally, patients who experience a sudden loss of vision are advised to cease use of semaglutide and promptly contact their doctors to discuss alternative treatment options.⁵

REFERENCES

1. Diabetes and your eyes: what you need to know. John Hopkins Medicine. Accessed July 16, 2024. https://www.hopkinsmedicine.org/health/conditions-and-diseases/diabetes-and-your-eyes-what-you-need-to-know
2. Semaglutide injection. Cleveland Clinic. Accessed July 16, 2024. https://my.clevelandclinic.org/health/drugs/19011-semaglutide-injection
3. Non-arteritic anterior ischemic optic neuropathy (naion). Brigham and Women’s Hospital. Accessed July 16, 2024. https://www.brighamandwomens.org/neurology/neuro-ophthalmology/non-arteritic-anterior-ischemic-optic-neuropathy#:~:text=Non%2Darteritic%20anterior%20ischemic%20optic%20neuropathy%20(NAION)%20refers%20to,one%20eye%2C%20without%20any%20pain.
4. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. July 3, 2024. doi:10.1001/jamaophthalmol.2024.2296
5. American academy of ophthalmology and north american neuro-ophthalmology society issue advice on weight loss drug and eye health. American Academy of Opthalmology. July 8, 2024. Accessed July 16, 2024. https://www.aao.org/newsroom/news-releases/detail/weight-loss-drug-and-eye-health