INTRODUCTION: Although the association between semaglutide use for diabetes or obesity and non-arteritic ischemic optic neuropathy (NAION) has been investigated, the relative risk has not been established in large, racially diverse populations. Given the increasing use of glucagon-like peptide 1 receptor agonist (GLP-1 RA) medications, it is vital to study the odds of this serious adverse event.
MATERIALS AND METHODS: We conducted a retrospective cohort study to investigate the relationship between semaglutide use and NAION in Military Health System beneficiaries ages 18 and older with diabetes or overweight and obesity who received care from December 7, 2017 to September 30, 2023. A subset analysis was performed using phosphodiesterase-5 inhibitors. This study was carried out as part of the Burden of Diseases and Injuries in the U.S. Military Health System, 2001-2018: Incidence, Prevalence, and Years Lived project and was found exempt by the Institutional Review Board at the Uniformed Services University of the Health Sciences.
RESULTS: A total of 1,212,775 individuals (973,529 patients with type 2 diabetes and 239,246 with overweight or obesity) were included. There were 2,447 NAION events identified. After adjusting for comorbidities, patients with type 2 diabetes prescribed semaglutide had a significantly lower risk of NAION (OR = 0.36, 95% CI = 0.25-0.51) compared to those prescribed non-GLP-1 RA medications. Among patients who had overweight or obesity, there was no significant difference in the odds of receiving a NAION diagnosis (OR = 0.10, 95% CI = 0.01-1.35). Use of phosphodiesterase-5 inhibitors was associated with lower odds of NAION in both populations (Type 2 diabetes: OR = 0.78, 95% CI = 0.69-0.87; overweight/obesity: OR = 0.49, 95% CI = 0.26-0.93) compared with those who did not use these medications.
CONCLUSION: This retrospective cohort study found a lower risk of NAION in patients with type 2 diabetes taking semaglutide compared with those taking non-GLP-1 RA medications in a large, diverse population. There was no association between NAION and semaglutide use in patients with overweight or obesity. These findings suggest that the risk of NAION should not preclude the use of this medication.