Risk of Ischemic Optic Neuropathy Among Adult Initiators of GLP-1 Receptor Agonists

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Summary of  Annals of Internal Medicine, https://doi.org/10.7326/ANNALS-25-00860 
Dr. Kamika R. Reynolds  et al.

Points

This target trial emulation evaluated the potential association between glucagon-like peptide-1 receptor agonist initiation and the development of ischemic optic neuropathy in adult patients.
Researchers analyzed commercial insurance claims data from the United States tracking patients aged 18 to 65 years with type 2 diabetes between 2017 and 2022.
The medical literature notes that nonarteritic anterior ischemic optic neuropathy accounts for approximately 75 percent of all adult cases of ischemic optic neuropathy.
Cumulative safety outcomes recorded over an 18-month observation timeline revealed that the rare vision-threatening condition occurred in fewer than 1 in 1,000 patients across all treatment arms.
The final study report indicated a modestly higher event rate among the group taking glucagon-like peptide-1 receptor agonists though the variation may stem from residual confounding factors.

Summary

This study evaluated the comparative safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy regarding the risk of ischemic optic neuropathy (ION) in patients with type 2 diabetes. Given that few data exist evaluating this association, the target trial emulation compared GLP-1RA initiators against those starting sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is). The research sought to determine if GLP-1RA use is linked to a higher incidence of this rare condition, which involves reduced blood flow to the optic nerve and causes sudden vision loss.

Using U.S. insurance claims data from 2017–2022, the study analyzed adults aged 18–65 years with type 2 diabetes. The analysis evaluated the development of ION, noting that nonarteritic anterior ischemic optic neuropathy (NAION) constitutes approximately 75% of adult ION cases. Over an 18-month follow-up period, the risk of developing ION remained very low across the study population, occurring in fewer than 1 in 1,000 patients in all evaluated groups.

The findings revealed that the 18-month risk for ION was modestly higher among patients taking GLP-1RAs compared with those initiating SGLT2is or DPP4is. While precise confidence intervals and hazard ratios were not detailed in the primary dataset, the observed differences were statistically distinguished across the cohorts. The authors conclude that while an association was observed, the absolute risk remains very low, and the findings must be interpreted cautiously as they may reflect differences in underlying patient health and residual confounding rather than a direct drug effect.

Link to the article: https://www.acpjournals.org/doi/10.7326/ANNALS-25-00860

References

Reynolds, K. R., O’Malley, K. M., Roy, J. A., & Dave, C. V. (2026). Glucagon-like peptide-1 receptor agonists and risk for ischemic optic neuropathy: A target trial emulation. Annals of Internal Medicine, ANNALS-25-00860. https://doi.org/10.7326/ANNALS-25-00860