Semaglutide use linked with increased risk for NAION in patients with diabetes
Key takeaways:
- The large-scale study focused on use of semaglutide and non-GLP-1 RAs.
- An increased risk for nonarteritic anterior ischemic optic neuropathy with semaglutide was seen at 2, 3 and 4 years from the index date.
In patients with diabetes, semaglutide use was associated with an increased risk for nonarteritic anterior ischemic optic neuropathy, according to a study published in JAMA Ophthalmology.
As Healio previously reported, this potential link was observed in a study by Jimena Tatiana Hathaway, MD, MPH, and colleagues. The findings were limited, however, by a small sample size of 710 patients from a single institution, Alan Y. Hsu, MD, of the department of ophthalmology at China Medical University Hospital in Taiwan, and colleagues wrote in the current study.
“Therefore, our study used the TriNetX global electronic health registry to assess the potential risk of NAION among patients with diabetes, using an alternative approach designed to address the limitations from previous studies such as that by Hathaway et al.,” they wrote.
The retrospective cohort study used the registry to identify 3,344,205 patients with diabetes and no history of nonarteritic anterior ischemic optic neuropathy (NAION) before taking semaglutide, using data collected between Oct. 1, 2019, and Dec. 31, 2023. A semaglutide group of 174,584 patients (51.8% women, 41.1% men) was compared with a control group of 174,584 patients (51.82% women, 41.24% men) that received non-glucagonlike peptide 1 receptor agonist (non-GLP-1 RA) medications.
In the patients treated with semaglutide, there was no increased risk for NAION at 1 month (HR = 2.99; 95% CI, 0.31-28.75), 3 months (HR = 1.33; 95% CI, 0.3-5.93), 6 months (HR = 1.79; 95% CI, 0.6-5.35) or 1 year (HR = 1.94; 95% CI, 0.93-4.02) after the index date compared with the non-GLP-1 RA medication group. There was an increased risk, however, at 2 years (HR = 2.39; 95% CI, 1.37-4.18), 3 years (HR = 2.44; 95% CI, 1.44-4.12) and 4 years (HR = 2.05; 95% CI, 1.26-3.34).
In a subgroup analysis of based on different semaglutide medications, there was an increased risk for NAION in patients who received stand-alone Ozempic (semaglutide, Novo Nordisk) (HR = 6.27; 95% CI, 2.92-13.47) or had a history of Ozempic use (HR = 2.47; 95% CI, 1.5-4.09) compared with those treated with non-GLP-1 RA medications.
Additionally, patients who received semaglutide and had concomitant hypertension demonstrated an increased risk for NAION (HR = 2.42; 95% CI, 1.19-4.92).
Notably, Hsu and colleagues reported that the increased risk for NAION was found only in women with diabetes who received semaglutide vs. those who received a non-GLP-1 RA medication.
“This stands in contrast to the result by Hathaway et al., where they found a sizable relationship between male sex and NAION risk among patients with diabetes who received semaglutide only,” they wrote. “Sex differences may help explain these findings, as certain diabetes-related complications, such as coronary artery disease, tend to be more prevalent in men, whereas conditions like retinopathy are more commonly observed in women.”
Reference:
Perspective
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Nonarteritic anterior ischemic optic neuropathy (NAION) is a relatively rare neuro-ophthalmic condition, occurring in between two to 10 people per 100,000 in the general population. NAION typically occurs in people aged older than 50 years, with type 2 diabetes being a strong risk factor. Recently, there have been reports of prescriptions of synthetic incretin mimetics being associated with the development of ischemic optic neuropathy. Following the seminal report that observed a potential association between the use of semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), and a diagnosis of NAION, there have been an increasing number of big data studies evaluating this potential association with conflicting findings.
Hsu and colleagues present a further retrospective big data study leveraging deidentified patient records from the U.S. research network included in the TriNetX analytics platform. They evaluated the strength of the association between semaglutide and ischemic optic neuropathy in people living with type 2 diabetes. To do this, they compared those prescribed a GLP-1 RA to those prescribed other diabetes medications. The primary analysis was appropriately propensity adjusted for demographics and the commonly expected risks associated with NAION among new users of semaglutide. What was surprising was that in their main analysis, they found no increased association within the first year of being prescribed semaglutide. However, they did note an increased hazard ratio between 2 years and 4 years. Other notable features found in the subgroup analyses were that the association was most commonly seen in people with concomitant hypertension and in those aged between 40 and 64 years. These findings may point to a potential plausible biological mechanism related to control of type 2 diabetes in a person with concurrent artherosclerotic disease in an already at-risk age group for NAION.
Many millions of people use GLP-1 RA medicines throughout the world due to their significant health benefits. Any person on a GLP-1 RA who has an acute change in their vision should be assessed rapidly. If they are found to have an ischemic optic neuropathy, the decision to stop or halt treatment for diabetic management should be made on a case-by-case basis. The evidence is evolving rapidly and weighing up risk vs. benefit is always best done in conjunction with the patient’s wishes and their endocrinologist.
References:Hathaway JT, et al. JAMA Ophthalmol. 2024;doi:10.1001/jamaophthalmol.2024.2296.
Hsu AY, et al. JAMA Ophthalmol. 2025;doi:10.1001/jamaophthalmol.2025.0349.
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