Semaglutide associated with increased cases of optic neuropathy, study finds
An observational study suggests a potential risk of nonarteritic anterior ischemic optic neuropathy associated with semaglutide, but more research is needed to assess causality, the study authors said.
A matched cohort study found higher risk of nonarteritic anterior ischemic optic neuropathy (NAION) in patients using semaglutide compared with patients prescribed non–glucagon-like peptide (GLP-1) receptor agonists.
The retrospective study used a centralized registry of patients evaluated by neuro-ophthalmologists at a single academic institution from December 2017 through November 2023. Propensity matching was used to assess whether semaglutide was associated with NAION in patients with type 2 diabetes or overweight/obesity, accounting for sex, age, systemic hypertension, diabetes, obstructive sleep apnea, obesity, hyperlipidemia, and coronary artery disease, as well as contraindications to semaglutide. Results were published by JAMA Ophthalmology on July 3.
Among 16,827 patients, 710 had type 2 diabetes (194 prescribed semaglutide, 516 prescribed non–GLP-1 antidiabetic medications) and 979 were overweight or obese (361 prescribed semaglutide, 618 prescribed non–GLP-1 weight-loss medications). In patients with diabetes, 17 NAION events occurred in patients prescribed semaglutide compared to six in the non–GLP-1 receptor agonist cohort. The cumulative incidence of NAION for the semaglutide and non–GLP-1 receptor agonist cohorts over 36 months was 8.9% (95% CI, 4.5% to 13.1%) and 1.8% (95% CI, 0% to 3.5%), respectively, which worked out to a significantly higher risk of NAION for patients receiving semaglutide (hazard ratio [HR], 4.28; [95% CI, 1.62 to 11.29]; P<0.001).
In the population of patients who were overweight or obese without diabetes, 20 NAION events occurred in the semaglutide cohort compared to three in the non–GLP-1 receptor agonist cohort. The cumulative incidence of NAION was 6.7% (95% CI, 3.6% to 9.7%) with semaglutide compared to 0.8% (95% CI, 0% to 1.8%) in the non–GLP-1 receptor agonist cohort over 36 months, also resulting in a significantly higher risk with semaglutide (HR, 7.64 [95% CI, 2.21 to 26.36]; P<0.001).
An editorial commended the authors for their work and noted that the results need to be replicated, and that future studies should examine the risk of repeat events or second eye involvement, which would add weight to the evidence of association and inform whether drug cessation is needed. Studies should also examine whether this effect occurs with all GLP-1 receptor agonists.
"Given the numbers of participants who have been recruited to clinical trials and the large number of people globally who use GLP-1 RAs [receptor agonists], we should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare," the editorial stated. "The potential risk of NAION should not deter the directed use of GLP-1 RA in [type 2 diabetes] or in people living with obesity, at this time."