No Association Between Semaglutide and Ischemic Optic Neuropathy, Study Suggests

A recent multinational, population-based, retrospective cohort study has indicated that semaglutide may not be associated with increased risks of nonarteritic anterior ischemic optic neuropathy (NAION).1

NAION is a common cause of vision loss, generally manifesting as isolated, painless, and sudden monocular vision loss with edema of the optic disc. Additionally, risk factors of NAION overlap significantly with those cerebrovascular disease. NAION results from a decrease in blood flow to the optic nerve head, which triggers optic disc swelling. Typically, patients experience progressive worsening of vision over a period of days or weeks, likely related to worsening ischemia.2

Semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), has emerged as a common and efficacious treatment for type 2 diabetes mellitus (T2DM), as well as maintaining cardiovascular health and promoting weight loss. A recent cohort study, however, has suggested that semaglutide may be associated with an increased risk of NAION.1

“To investigate the association between the use of semaglutide and the risk of NAION in the general population, we conducted a cohort study using TriNetX, a global network that encompasses patients from 21 countries,” wrote Chien-Chih Chou, MD, PhD, National Yang Ming Chiao Tung University, and colleagues. “The aim of our study was to assess whether semaglutide poses a risk for NAION across a broader population worldwide.”1

The team collected data on adults ≥18 years with T2DM or obesity who had visited healthcare organizations ≥3 times. A total of 297,220 participant profiles were included, which were then split into three cohorts. 37,314 participants had only T2DM (and a BMI <30 kg/m2), 129,690 had only obesity (and BMI ≥30 kg/m2), and 130,216 had both conditions (T2DM and a BMI ≥30 kg/m2). Each cohort was then further grouped into those prescribed semaglutide and those using non-GLP-1RA glucose-lowering or weight loss medication.1

The T2DM-only group had a mean age (standard deviation [SD]) of 63.2 (11.3) years in those using semaglutide and 62.9 (12.3) in those using non-GLP-1RA medications. The patients exhibited ≤10 cases of NAION, both in those using semaglutide and GLP-1RAs after a year. NAION occurred in 12 and ≤10 cases after 2 years and 14 and 13 after 3.1

Semaglutide was not associated with increased risk of NAION in the T2DM cohort across 1-year (HR 2.32; 95% CI, .60-8.97), 2-year (HR 2.31; 95% CI, .86-6.17) and 3-year (HR 1.51; 95% CI, .71-3.25) follow-up periods. Sensitivity analysis also indicated no increased risk of NAION compared with GLP-1RA glucose-lowering medications (HR 1.20; 95% CI, .62-2.33) among the T2DM-only cohort.1

The obesity-only group had a mean age (SD) of 48 (13.3) years for semaglutide and 48.1 (13.7) years for non-GLP-1RAs. After all three follow-up periods, ≤10 NAION events occurred across both cohorts. The difference was not significant across each period (1-year: HR 0.41; 95% CI, .08-2.09; 2-year: HR .67; 95% CI, .20-2.24; 3-year: HR .72; 95% CI, .24-2.17). Sensitivity analysis showed consistent relationships between semaglutide and NAION (HR .46; 95% CI, .15-1.47).1

The T2DM with obesity cohort had a mean age (SD) of 58.7 (12) years in semaglutide and 58.5 (13.1) years in non-GLP-1RA. After 1 year, 16 patients in the semaglutide group and 20 in the non-GLP-1RA group developed NAION (HR .81; 95% CI, .42-1.57). NAION developed in 34 cases using semaglutide and 33 using non-GLP-1RAs over 2 years (HR 1.2; 95% CI, .74-1.94) and in 41 cases using semaglutide and 47 using non-GLP-1RAs over 3 years (HR 1.19; 95% CI .78-1.82). Sensitivity analysis showed no association between semaglutide use and NAION risk (HR 1.05; 95% CI, .67-1.64).1

Chou and colleagues noted that these results showed no significant association between semaglutide use and an increased risk of NAION when compared to non-GLP-1RAs. Subgroups, particularly those with different baseline comorbidities and across different follow-up periods, also exhibited no association. The large sample size included by the team indicates a potential applicability to the general population.1

“Semaglutide should be used judiciously because its benefits in improving glucose control and cardiovascular health outweigh its potential risks associated with NAION,” wrote Chou and colleagues. “Large prospective cohort studies or clinical trials are necessary to obtain more conclusive evidence.”1

References

1. 1: Chou C-C, Pan S-Y, Sheen Y-J, et al. Association between semaglutide and nonarteritic anterior ischemic optic neuropathy. Ophthalmology. 2024;132(4):381-388. doi:10.1016/j.ophtha.2024.10.030

2. 2: Biousse V, Newman NJ. Ischemic optic neuropathies. New England Journal of Medicine. 2015;372(25):2428-2436. doi:10.1056/nejmra1413352