Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

Chien-Chih Chou; Ssu-Yu Pan; Yi-Jing Sheen; Jun-Fu Lin; Chien-Heng Lin; Hui-Ju Lin; I-Jong Wang; Chien-Hsiang Weng

doi:10.1016/j.ophtha.2024.10.030

Association between Semaglutide and Non-Arteritic Anterior Ischemic Optic Neuropathy: A Multinational Population-Based Real-World Study

Ophthalmology. 2024 Nov 2:S0161-6420(24)00685-7. doi: 10.1016/j.ophtha.2024.10.030. Online ahead of print.

Authors

Chien-Chih Chou¹, Ssu-Yu Pan², Yi-Jing Sheen³, Jun-Fu Lin⁴, Chien-Heng Lin⁵, Hui-Ju Lin⁶, I-Jong Wang⁷, Chien-Hsiang Weng⁸

Affiliations

¹ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
² School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Ophthalmology, Taichung Veterans General Hospital, Taichung, Taiwan.
³ School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; Center for Quantitative Imaging in Medicine (CQUIM), Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁴ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
⁵ Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung, Taiwan; Institute of Public Health and Community Medicine Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁶ Eye Center, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
⁷ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan; Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
⁸ Department of Family Medicine, Brown University Warren Alpert Medical School, Providence, Rhode Island, USA; Coastal Medical Lifespan, Providence, Rhode Island, USA. Electronic address: chien-hsiang_weng@brown.edu.

PMID: 39491755
DOI: 10.1016/j.ophtha.2024.10.030

Abstract

Objective: To investigate whether semaglutide increases the risk of non-arteritic anterior ischemic optic neuropathy (NAION) in the general population.

Design: This retrospective cohort study utilized a de-identified global electronic medical records database. The enrollment period was extended from January 2017 to August 2023, with observations concluding in August 2024.

Participants: This study included individuals with type 2 diabetes mellitus (T2DM) or obesity. They were further categorized into T2DM-only, obesity-only, and T2DM with obesity groups to assess the differences among these subgroups. The effects of semaglutide were compared with those of glucose-lowering or weight loss medications other than glucagon-like peptide receptor agonists.

Methods: Patient data were obtained from 160 healthcare organizations across 21 countries. Outcomes were evaluated at one, two, and three years of follow-up. A 1:1 propensity score matching was performed to balance age, sex, body mass index, hemoglobin A1C, medications, and underlying comorbidities. Cox regression models were used to compute hazard ratios (HR) and 95% confidence intervals (CI).

Main outcome measures: The occurrence of NAION.

Results: The final analysis included 37,245 participants with T2DM-only, 33,537 participants with obesity-only, and 64,989 participants with both T2DM and obesity. The results indicated that the administration of semaglutide was not associated with the development of NAION in the T2DM-only group (1 year follow-up: HR, 2.32; 95% CI, 0.60-8.97; 2 years: HR, 2.31; 95% CI, 0.86-6.17; 3 years: HR, 1.51; 95% CI, 0.71-3.25), the obesity-only group (1 year follow-up: HR, 0.25; 95% CI, 0.03-2.28; 2 years: HR, 0.44; 95% CI, 0.09-2.21; 3 years: HR, 0.44; 95% CI, 0.09-2.21), and the T2DM with obesity group (1 year follow-up: HR, 0.81; 95% CI, 0.42-1.57; 2 years: HR, 1.2; 95% CI, 0.74-1.94; 3 years: HR, 1.19; 95% CI, 0.78-1.82).

Conclusions: The findings suggest that semaglutide may not be associated with an increased risk of NAION in the general population. Therefore, avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.

Keywords: non-arteritic anterior ischemic optic neuropathy; semaglutide; stroke.