A recent study conducted at a prominent academic medical institution suggests a potential link between the prescription of semaglutide, a popular glucagon-like peptide 1 receptor agonist (GLP-1 RA), and an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION). The findings highlight the need for further investigation to assess causality and explore the implications for patients with type 2 diabetes (T2D) and obesity.
Key Findings from the Study
Researchers analyzed data from 16,827 patients over six years, focusing on individuals with T2D or who were overweight or obese. The study revealed that patients prescribed semaglutide exhibited a significantly higher incidence of NAION compared to those prescribed non–GLP–1 RA medications.
For patients with T2D, the cumulative 36-month incidence of NAION was 8.9% among those taking semaglutide, compared to 1.8% for those on other diabetes medications. The hazard ratio (HR) indicated a 4.28-fold higher risk of NAION in the semaglutide cohort. Similarly, among overweight or obese patients, the NAION incidence was 6.7% in the semaglutide group versus 0.8% in the comparison group, with an HR of 7.64.
Study Design and Methods
The retrospective study utilized a centralized clinical data registry and involved patients evaluated by neuro-ophthalmologists between December 2017 and November 2023. Researchers applied International Classification of Diseases (ICD-10) code H47.01 to identify cases of ischemic optic neuropathy, confirmed through manual reviews of medical records.
Using propensity score matching, the study compared semaglutide users with patients prescribed alternative medications while controlling for covariates such as age, sex, systemic conditions (hypertension, obstructive sleep apnea, coronary artery disease), and other potential risk factors for NAION.
Data analysis involved the Kaplan-Meier method to estimate cumulative incidences and Cox proportional hazards regression models to evaluate the association between semaglutide prescriptions and NAION risk.
Semaglutide: A Rising Star with Concerns
Semaglutide, marketed as Ozempic and Wegovy by Novo Nordisk, has become increasingly popular for managing T2D and obesity. Since its FDA approval in 2017 for diabetes and 2022 for weight loss, semaglutide prescriptions have surged by 60% between 2021 and 2023. Its efficacy in glycemic control and weight management has made it a cornerstone treatment, but the study’s findings suggest the need for caution.
The study also emphasized the role of neuro-ophthalmologists in identifying NAION cases, given its status as the second most common optic neuropathy and a significant cause of adult blindness.
Implications and Future Directions
While the study highlights a concerning association between semaglutide and NAION, it stops short of establishing causality. The researchers recommend larger, multicenter cohort studies and randomized clinical trials to validate these findings and investigate the underlying mechanisms.
Challenges remain in conducting larger studies, including the lack of a specific ICD-10 code for NAION and the potential for diagnostic inaccuracies in extensive datasets. Emerging algorithms may improve diagnostic precision but cannot yet match the accuracy of manual record reviews.
 Balancing Benefits and Risks
Semaglutide’s rising popularity underscores its effectiveness in managing T2D and obesity, but the potential risk of NAION calls for careful patient monitoring. This study serves as a crucial first step in understanding the broader implications of GLP-1 RA drugs on ocular health.
For healthcare providers, the findings emphasize the importance of informed decision-making and vigilance when prescribing semaglutide, particularly for patients with pre-existing risk factors for NAION. As further research unfolds, balancing the benefits of semaglutide with its potential risks will be critical in optimizing patient outcomes.