Study Disputes Link Between GLP-1 Drugs and Higher Optic Neuropathy Risk

This study did not corroborate previous results that linked GLP-1 agonists to a higher optic neuropathy risk in obese patients or those with type 2 diabetes. Photo: JNeil Miller, MD. Click image to enlarge. Another new study weighs in on the effects—good and bad—of glucagon-like peptide-1 (GLP-1) receptor agonist drugs and the eye. Although several recent studies have explored the potential association between GLP-1 agents and nonarteritic ischemic optic neuropathy (NAION), the literature on this matter remains contradictory. In a recent study, Brazilian researchers investigated the potential association between GLP-1 therapy and optic neuropathy in adults with type 2 diabetes and obesity; they found that events were rare, supporting the ocular safety of GLP-1 therapy. The team’s findings were published in AJO International.Subjects were stratified according to exposure to GLP-1 or other glucose-lowering therapies. Patients with diagnostic codes for giant cell arteritis were excluded. The primary outcome was ischemic optic neuropathy, identified using ICD-10 code H47.01. Propensity score matching was performed for demographic characteristics, comorbidities, laboratory variables, insulin and antihypoglycemic medication use and medications associated with optic neuropathy risk, including amiodarone, sildenafil and tadalafil.A total of 205,500 patients were included in each cohort (GLP-1 users and a non-GLP-1 comparator). The study findings support the overall ocular safety of this drug class, as the absolute frequency of events remained very low, occurring in 134 patients (0.065%) in the GLP-1 agonist cohort and 143 patients (0.07%) in the comparator cohort.Cumulative risk analysis showed no statistically significant difference between the cohorts (risk ratio 0.937). Kaplan-Meier analysis indicated survival probabilities of 99.86% for the GLP-1 group and 99.9% for the comparator group. While cumulative risk did not differ significantly, regression analysis suggested a modestly higher hazard ratio of 1.271.“This combination of findings supports a balanced interpretation,” the researchers wrote; although NAION events were rare among GLP-1 receptor agonist users, “the possibility of small risk differences, particularly with specific agents or in selected high-risk patients, remains clinically relevant.”The biological relationship between GLP-1 agonist therapy and optic nerve ischemia remains uncertain. Large cardiovascular trials have demonstrated that liraglutide and semaglutide reduce major  cardiovascular adverse events without a consistent signal of increased microvascular complications, the researchers explained in the paper. Experimental and translational studies have suggested that GLP-1 drugs may improve endothelial function, nitric oxide signaling, oxidative stress and microvascular recruitment, they elaborated.“Because optic nerve ischemia is closely related to vascular dysregulation and impaired perfusion, these mechanisms provide a biologically plausible rationale for studying this question,” the authors explained in their paper. “However, the optic nerve may be uniquely vulnerable to changes in perfusion, autoregulation, metabolic status and local anatomic susceptibility, and favorable systemic vascular effects may not necessarily translate into reduced optic nerve ischemic risk.”Beyond their cardiovascular benefits, GLP-1 agents may also influence ocular microvascular physiology. A previous study highlighted that they increase nitric oxide production, reduce oxidative stress and promote microvascular recruitment, including in the retina and optic nerve, through direct actions on vascular endothelium. In clinical settings, a separate study showed that GLP-1 infusion significantly improved endothelial function in patients with type 2 diabetes and coronary artery disease, reinforcing the microvascular potential of this class. From a clinical perspective, these findings should be interpreted alongside the established cardiometabolic benefits of GLP-1 receptor agonists and the evolving ocular safety literature. “The low absolute event frequency observed in both cohorts suggests that optic nerve ischemic events are uncommon in this population,” the authors wrote in their paper. “However, given the potential severity of NAION and related IONs, clinicians should remain attentive to acute visual symptoms,” especially those with vascular risk factors. They added that future studies with agent-specific exposure assessment and clinically adjudicated ophthalmic outcomes are needed to clarify whether the signals observed across recent studies reflect causal risk, residual confounding or differences in study design.Click here for the journal source. Andreao FF, Amaral DC, Machado Magalhaes PL, et al. GLP-1 receptor agonists and ischemic optic neuropathy in patients with type 2 diabetes and obesity: a TriNetX Cohort study. AJO International. June 10, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.