GLP-1 Drugs May Modestly Raise Optic Neuropathy Risk in T2D

TOPLINE:

A large cohort study found that the use of GLP-1 receptor agonists (GLP-1 RAs) over 3 years was associated with a modestly increased risk for nonarteritic anterior ischemic optic neuropathy (NAION) compared with the use of SGLT2 inhibitors in veterans with type 2 diabetes (T2D).

METHODOLOGY:

• Pharmacovigilance reports and emerging, but inconsistent, population-based studies suggest that the use of GLP-1 RAs may be linked to ocular adverse events, including a possible increased risk for NAION; however, it remains unclear whether the association is specific to NAION as compared with other optic disorders.
• Researchers conducted a target trial emulation study using nationwide electronic health records from the US Department of Veterans Affairs to compare the 3-year risk for NAION among veterans with T2D who initiated GLP-1 RAs vs SGLT2 inhibitors.
• The study included 588,168 veterans with T2D, of whom 139,546 initiated GLP-1 RA therapy (mean age, 65.33 years; 90.2% male) and 448,622 initiated SGLT2 inhibitor therapy (mean age, 67.94 years; 95.3% male) between 2017 and 2024; groups were subsequently matched using propensity score-based inverse probability weighting.
• Cases of NAION were identified from medical records using standard diagnostic codes; cases diagnosed by an eye care specialist and repeat diagnoses were also evaluated.
• The 3-year cumulative incidence, cumulative incidence difference (CID), and cumulative incidence ratio of NAION were estimated.

TAKEAWAY:

• Over 3 years, individuals who started GLP-1 RAs had a small but statistically significant increase in the risk for NAION compared with those who started SGLT2 inhibitors — 39.07 vs 29.33 cases per 10,000 people (CID, 9.98 per 10,000 people; 95% CI, 3.48-14.03) — and a relative increase of about 35% (cumulative incidence ratio, 1.35; 95% CI, 1.11-1.51).
• The increased risk for NAION with the use of GLP-1 RAs was consistent across definitions: diagnosis by an eye care specialist (CID, 8.73; 95% CI, 2.46-12.89), repeat diagnoses (CID, 6.35; 95% CI, 2.40-9.65), and repeat diagnoses with a specialist (CID, 5.91; 95% CI, 2.00-8.88).
• Compared with the use of SGLT2 inhibitors, the use of GLP-1 RAs was not associated with an increased risk for other optic disorders such as diabetic retinopathy, macular degeneration, retinal vascular occlusion, or optic neuritis.
• The frequency of ophthalmology or optometry clinic visits during follow-up was found to be similar between the two groups, suggesting that the association with NAION was not due to differential surveillance.

IN PRACTICE

“GLP-1 RA use was associated with a modestly increased risk of NAION compared with [SGLT2 inhibitor] use. While the absolute risk remains low, the specificity of this finding may warrant heightened vigilance,” the authors of the study wrote.

SOURCE:

The study was led by Taeyoung Choi, MS, Clinical Epidemiology Center, Research and Development Service, VA St Louis Health Care System, St. Louis. It was published online on April 30, 2026, in JAMA Network Open.

LIMITATIONS:

The study cohort was older and predominantly male, limiting generalizability to other populations. Residual confounding, selection bias, and outcome misclassification could not be fully excluded.

DISCLOSURES:

The study was funded by the US Department of Veterans Affairs. Two authors reported being uncompensated consultants for Pfizer.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

A version of this article first appeared on Medscape.com.