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Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide
TAKE-HOME MESSAGE
- This retrospective cohort study investigated the association between semaglutide use and the risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients with type 2 diabetes or overweight/obesity. A significantly higher number of NAION events occurred in semaglutide cohorts than in non–GLP-1 receptor agonist antidiabetes cohorts across both populations with type 2 diabetes and overweight/obesity. The cumulative incidence of NAION over 36 months was also significantly higher in semaglutide cohorts. A Cox proportional hazards regression model showed a higher risk of NAION among patients receiving semaglutide.
- These findings suggest a potential risk of NAION associated with the use of semaglutide; however, further research is warranted to assess causality.
abstract
This abstract is available on the publisher's site.
Access this abstract nowIMPORTANCE
Anecdotal experience raised the possibility that semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1 RA) with rapidly increasing use, is associated with nonarteritic anterior ischemic optic neuropathy (NAION).
OBJECTIVE
To investigate whether there is an association between semaglutide and risk of NAION.
DESIGN, SETTING, AND PARTICIPANTS
In a retrospective matched cohort study using data from a centralized data registry of patients evaluated by neuro-ophthalmologists at 1 academic institution from December 1, 2017, through November 30, 2023, a search for International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code H47.01 (ischemic optic neuropathy) and text search yielded 16 827 patients with no history of NAION. Propensity matching was used to assess whether prescribed semaglutide was associated with NAION in patients with type 2 diabetes (T2D) or overweight/obesity, in each case accounting for covarying factors (sex, age, systemic hypertension, T2D, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease) and contraindications for use of semaglutide. The cumulative incidence of NAION was determined with the Kaplan-Meier method and a Cox proportional hazards regression model adjusted for potential confounding comorbidities. Data were analyzed from December 1, 2017, through November 30, 2023.
EXPOSURES
Prescriptions for semaglutide vs non-GLP-1 RA medications to manage either T2D or weight.
MAIN OUTCOMES AND MEASURES
Cumulative incidence and hazard ratio of NAION.
RESULTS
Among 16 827 patients, 710 had T2D (194 prescribed semaglutide; 516 prescribed non-GLP-1 RA antidiabetic medications; median [IQR] age, 59 [49-68] years; 369 [52%] female) and 979 were overweight or obese (361 prescribed semaglutide; 618 prescribed non-GLP-1 RA weight-loss medications; median [IQR] age, 47 [32-59] years; 708 [72%] female). In the population with T2D, 17 NAION events occurred in patients prescribed semaglutide vs 6 in the non-GLP-1 RA antidiabetes cohort. The cumulative incidence of NAION for the semaglutide and non-GLP-1 RA cohorts over 36 months was 8.9% (95% CI, 4.5%-13.1%) and 1.8% (95% CI, 0%-3.5%), respectively. A Cox proportional hazards regression model showed higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; 95% CI, 1.62-11.29); P < .001). 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. The cumulative incidence of NAION for the semaglutide vs non-GLP-1 RA cohorts over 36 months was 6.7% (95% CI, 3.6%-9.7%) and 0.8% (95% CI, 0%-1.8%), respectively. A Cox proportional hazards regression model showed a higher risk of NAION for patients prescribed semaglutide (HR, 7.64; 95% CI, 2.21-26.36; P < .001).
CONCLUSIONS AND RELEVANCE
This study's findings suggest an association between semaglutide and NAION. As this was an observational study, future study is required to assess causality.
Additional Info
Disclosure statements are available on the authors' profiles:
Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide
JAMA Ophthalmol 2024 Jul 03;[EPub Ahead of Print], JT Hathaway, MP Shah, DB Hathaway, SM Zekavat, D Krasniqi, JW Gittinger, D Cestari, R Mallery, B Abbasi, M Bouffard, BK Chwalisz, T Estrela, JF RizzoFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The study is a retrospective observational review of the risk of nonarteritic anterior ischemic optic neuropathy (NAION) associated with the use of semaglutide. After 16,827 charts of patients referred to one neuro-ophthalmology academic center over a 6-year period were reviewed, they found 710 with type 2 diabetes and 979 with obesity. The authors found an increased risk of NAION with the use of semaglutide, particularly in the first year of use of medication. In matched groups, the risk with semaglutide for patients with type 2 diabetes was 8.9% versus 1.8% for non–GLP-1 receptor agonist exposure, whereas the risk for NAION for patients with obesity was 6.7% versus 0.8% for those not treated with semaglutide.
NAION is caused by an infarction in the optic nerve head, most likely at the level of the short posterior ciliary arteries. Risk factors include no or minimal cupping of the optic nerve head ("disc at risk"), vascular disease such as diabetes and hypertension, sleep apnea, nocturnal hypotension, and possibly medications such as phosphodiesterase type 5 inhibitors. The pathogenesis of the disease is still not completely understood. The authors speculate that perhaps GLP-1 receptor agonist medications might influence optic nerve head perfusion.
Strengths of the study include that all diagnoses of NAION were made by experienced neuro-ophthalmologists from one institution. All charts with diagnosis of NAION were manually reviewed to confirm diagnosis and to confirm that semaglutide had been dispensed. NAION occurred most frequently in the first year, suggesting an association with the use of the drug.
Limitations include that results may not be generalizable, since the study was conducted by a tertiary care institution. The study was retrospective and observational, and no review was done to confirm use of medication. The sample size seems small since, of the more than 16,000 patients, only 4% had diabetes and 5% had obesity. No mention was made of second-eye involvement, which is usually about 15%, nor was there mention of patients having a disc at risk.
NAION is relatively uncommon, occurring from 2 to 10 per 100,000 people per year. This study needs to be replicated in other settings with further evaluation of second-eye involvement. If this association is confirmed in other studies, patients should be evaluated by an ophthalmologist or by fundus photos to look for disc at risk. Patients should also be instructed to take blood pressure medication in the morning to avoid nocturnal hypotension and for physicians to control other variables as much as possible.