Study suggests potential link between semaglutide and risk of non-arteritic ischemic optic neuropathy

(Image credit: AdobeStock/Andreas Prott)

Boston researchers led by first author Jimena Tatiana Hathaway, MD, MPH, reported that there is a potential risk of the development of non-arteritic ischemic optic neuropathy (NAION)¹ associated with prescriptions for semaglutide (Wegovy, Ozempic, Novo Nordisk). Prescriptions with semaglutide are FDA approved to treat obesity and type 2 diabetes, respectively.

Hathaway is from the Harvard T.H. Chan School of Public Health, and the Department of Ophthalmology, and Neuro-Ophthalmology Service Massachusetts Eye and Ear, Harvard Medical School, all in Boston.

The authors cited anecdotal experience that suggested that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA), the use of which has been rapidly increasing, may be associated with the development of NAION.

They recognized that this association may be important considering that the weekly new-to-brand prescriptions in the US of these and other GLP-1 RA drugs have increased by about 60% from 2021 to 2023.²

In light of this, they conducted a retrospective matched-cohort study to determine if this association was valid. They searched a centralized data registry of patients who had undergone neuro-ophthalmologic evaluations at 1 academic institution from December 1, 2017, through November 30, 2023, for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) to identify patients.

They used propensity matching to determine if semaglutide was associated with NAION in patients who had type 2 diabetes or those who were overweight or obese. For each case, they accounted for covarying factors (sex, age, systemic hypertension, type 2 diabetes, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications to the use of semaglutide. All patients had been treated with semaglutide or a non–GLP-1 RA medications to manage type 2 diabetes or weight.

The main outcome measure was the cumulative incidence and hazard ratio of NAION.

Data analysis of the effects of semaglutide

Among the 1,689 study patients, 710 had type 2 diabetes and 979 were overweight or obese. Of those with type 2 diabetes, 194 had been treated with semaglutide and 516 with non–GLP-1 RA antidiabetic medications; of those who were overweight or obese, 361 had been treated with semaglutide and 618 with non–GLP-1 RA weight-loss medications.

In the patients with type 2 diabetes, the authors reported that “17 NAION events occurred in patients prescribed semaglutide vs 6 in the non–GLP-1 RA antidiabetes cohort. The cumulative incidence rates of NAION for the semaglutide and non–GLP-1 RA cohorts over 36 months were 8.9% (95% confidence interval [CI], 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively.”

The analysis showed that patients treated with semaglutide had a higher risk of developing NAION compared with non-GLP-1 RA antidiabetes medications (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < 0.001).

Among the patients who were overweight or obese, a similar picture emerged. The investigators reported that 20 NAION events occurred in patients treated with semaglutide compared with 3 in the non–GLP-1 RA cohort. This resulted in cumulative incidence rates of NAION for the semaglutide vs non–GLP-1 RA cohorts over 36 months of 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. This difference was also significant (HR, 7.64; 95% CI, 2.21-26.36; P <0 .001).

Hathaway and colleagues concluded, “This study’s findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.”

References:

1. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol. Published online July 3, 2024. doi:10.1001/jamaophthalmol.2024.2296

2. Novo Nordisk. Q1 2023 presentation, page 15. Accessed December 20, 2023. https://investor.novonordisk.com/q1-2023-presentation/?page=15