Glucagon-Like Peptide 1 Receptor Agonists and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients With Type 2 Diabetes

Feb 17, 2026Diabetes care

Glucagon-Like Peptide 1 Receptor Agonists and Risk of Sudden Optic Nerve Damage in People with Type 2 Diabetes

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Abstract

At 1 year, there were 14 NAION events among 106,858 GLP-1 RA initiators compared to 53 among 416,369 DPP-4 inhibitor initiators.

GLP-1 receptor agonists were associated with an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION) compared to DPP-4 inhibitors.
The relative risk of NAION for GLP-1 RA users was 2.56, indicating more than double the risk compared to those on DPP-4 inhibitors.
The risk difference was 11.3 NAION cases per 100,000 individuals, suggesting a notable increase in risk.
The increased risk of NAION was particularly pronounced during the first 6 months of GLP-1 RA use and tended to diminish with longer use.
Higher risks were observed in patients under 50 years of age, men, ever-smokers, and those who experienced a significant reduction in hemoglobin A1c.

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OBJECTIVE: To estimate the effect of initiating glucagon-like peptide 1 receptor agonists (GLP-1 RAs) versus dipeptidyl peptidase 4 (DPP-4) inhibitors on incident nonarteritic anterior ischemic optic neuropathy (NAION) among adults with type 2 diabetes.

RESEARCH DESIGN AND METHODS: This active-comparator, new-user cohort emulated a pragmatic target trial using the U.K. Clinical Practice Research Datalink. Patients aged ≥18 years with a physician diagnosis of type 2 diabetes who newly initiated a GLP-1 RA or a DPP-4 inhibitor were included. DPP-4 inhibitors were selected as the comparator because they may be used as second-line treatment, like GLP-1 RAs, and have no established association with NAION. We estimated risks, risk differences (RDs), and risk ratios (RRs) of incident NAION, adjusted using propensity-score fine-stratification weighting.

RESULTS: At 1 year, there were 14 NAION events among 106,858 GLP-1 RA initiators (18.5 per 100,000) and 53 among 416,369 DPP-4 inhibitor initiators (7.2 per 100,000). GLP-1 RAs were associated with an increased risk of NAION compared with DPP-4 inhibitors (RR 2.56; 95% CI 1.44-4.86; RD 11.3 per 100,000). The risk of NAION was higher during the first 6 months of use, diminishing with longer duration of use, and was higher in patients aged <50 years, men, ever-smokers, and those with ≥1% hemoglobin A1c reduction.

CONCLUSIONS: GLP-1 RAs were associated with an increased 1-year risk of NAION compared with DPP-4 inhibitors among adults with type 2 diabetes, particularly in younger patients, men, ever-smokers, and patients with a marked hemoglobin A1c reduction.