Semaglutide Use Increases Risk of Optic Neuropathy

Compared with individuals using non–glucagon-like peptide 1 receptor agonists (non–GLP-1 RAs), patients with type 2 diabetes and obesity who used the GLP-1 RA semaglutide experienced an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION).

“Spending on weight-loss drugs—originally marketed as diabetes treatments—will likely continue to climb as supplies catch up with the huge demand. The trend will escalate further as additional similar drugs come to market and as the FDA approves the medications for more conditions,” said Eric Tichy, PharmD, MBA, division chair of supply chain management at Mayo Clinic.¹

As the country’s demand for semaglutide and other GLP-1 RAs increases, much more has been discussed about these drugs’ potential to save lives rather than their potential to increase certain risk factors in patients with various comorbidities.

While researchers are now exploring the expanded benefits of GLP-1 RAs to treat conditions like Alzheimer disease and alcohol use disorder, it is important to understand these medications’ association with specific adverse events previously reported.²

One of those events included increased risk of gastrointestinal complications. According to a 2022 study, 11,326 semaglutide-related gastrointestinal adverse events were reported in 5442 patients.³

Despite gastrointestinal issues being common adverse effects for patients using semaglutide, a new possible event has garnered traction among patients with T2D or obesity looking to treat their conditions with semaglutide. Researchers have recently assessed the association between semaglutide use and the risk of nonarteritic anterior ischemic optic neuropathy (NAION), “the second most common form of optic neuropathy and a significant cause of blindness among adults,” according to a study published in JAMA Ophthalmology.⁴

The retrospective matched cohort study compared patients using semaglutide with those using non–GLP-1 RAs to treat either T2D or obesity. Among the study population and matched cohorts, 710 patients had T2D and 979 were overweight or had obesity. Of the 710 individuals with T2D, only 194 were prescribed semaglutide, while the other 516 patients were prescribed non–GLP-1 RA medications. Of the 979 individuals with obesity, 361 were prescribed semaglutide, while the other 618 received non-GLP-1 RAs.

Results were recorded in a neuro-ophthalmology clinic from December 2017 through November 2023.

“In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort,” wrote the authors.⁴ “In the population of patients who were overweight or obese, 20 NAION events occurred in the prescribed semaglutide cohort vs 3 in the non-GLP-1 RA cohort.”

This study, which is the first to report an association between NAION and semaglutide use, reported a significant link between the GLP-1 RA and adverse events of NAION.⁴ While this association has raised concerns of further risks highlighted by the use of semaglutide, it seems that its benefits are far exceeding that of the drug’s downsides. “Weekly new-to-brand prescriptions in the United States of these and other glucagon-like peptide receptor agonist (GLP-1 RA) drugs increased by approximately 60% from 2021 to 2023,” continued the authors.⁴

But as GLP-1 RAs continue to benefit the diabetes and overweight or obese communities, health care professionals are keeping an eye on these “life-saving” drugs and encouraging more research as new approvals continue to hit the supply chain.

“As with any drug, however, therapeutic benefits are inseparable from adverse effects. Related to vision, patients with diabetic retinopathy who received semaglutide incurred a higher risk of exacerbation of the retinopathy, especially with rapid reduction in hemoglobin A1c levels,” they wrote.⁴

With this being the first known study assessing the risks of using GLP-1 RAs, researchers agree that more research is needed to address the full extent of this association.

“Despite evidence of neuroprotective properties, expression of the GLP-1 receptor in the human optic nerve and GLP-1 RA-induced enhanced sympathetic nervous system activity might influence optic nerve head perfusion and potentially increase the risk of NAION…This study’s findings suggest an association between semaglutide and NAION. As this was an observational study, future [studies are] required to assess causality,” concluded the authors.⁴

READ MORE: Semaglutide Access, Cost Issues Could be Addressed With New DNA Test

References

1. Enormous demand for weight-loss drugs drives up total U.S. prescription spending. News release. American Society of Health System Pharmacists. April 24, 2024. Accessed July 8, 2024. https://www.prnewswire.com/news-releases/enormous-demand-for-weight-loss-drugs-drives-up-total-us-prescription-spending-302125178.html

2. Rubin R. Could GLP-1 receptor agonists like semaglutide treat addiction, Alzheimer disease, and other conditions? JAMA. 2024;331(18):1519–1521. doi:10.1001/jama.2024.1017

3. Shu Y, He X, Wu P, Liu Y, Ding Y, Zhang Q. Gastrointestinal adverse events associated with semaglutide: a pharmacovigilance study based on FDA adverse event reporting system. Front Public Health. 2022;10:996179. 2022 Oct 20. doi:10.3389/fpubh.2022.996179

4. 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