Glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischemic optic neuropathy: Evidence from a global real-world cohort

Feb 13, 2026Diabetes & metabolism

Glucagon-Like Peptide-1 Drugs and the Risk of Sudden Optic Nerve Damage: Evidence from Worldwide Patient Data

AI simplified

GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

Over 9 years, GLP-1 RA users showed a higher cumulative incidence of NAION at 0.21% compared to 0.17% in other antidiabetic users.

GLP-1 RA therapy is associated with a statistically significant increased risk of NAION.
Cox proportional hazards models indicated a hazard ratio of 1.38 when comparing GLP-1 RA users to other antidiabetic users.
A similar hazard ratio of 1.30 was observed when comparing GLP-1 RA users to SGLT-2 inhibitor users.
Kaplan-Meier curves demonstrated consistent early separation, indicating a higher risk for GLP-1 RA users.
Sensitivity analyses supported the observed patterns of increased risk.

AI simplified

AIMS: To evaluate whether GLP-1 RA therapy is associated with an increased risk of NAION in a large, diverse real-world population.

METHODS: This retrospective cohort study utilized the TriNetX U.S. Collaborative Network from 2015 to 2024. Adults (≥18 years) with type 2 diabetes mellitus (T2DM) were identified and grouped as GLP-1 RA users versus other antidiabetic users and GLP-1 RA users versus sodium-glucose cotransporter-2 inhibitors (SGLT-2 i) users. Patients with preexisting optic neuropathy or severe ocular disease were excluded. Propensity score matching (1:1) was applied to balance baseline characteristics. The primary outcome was incident NAION, defined by ICD-10 codes. Cox proportional hazards models and Kaplan-Meier analyses were used to estimate hazard ratios (HRs) and cumulative probabilities.

RESULTS: After matching, 799 036 GLP-1 RA users were compared with 799 036 other antidiabetic users, and 429 985 GLP-1 RA users were compared with 429 985 SGLT-2i users. Over 9 years, GLP-1 RA users showed higher cumulative NAION incidence vs other agents (0.21% vs 0.17%; HR 1.38; 95% CI, 1.23-1.55) and vs SGLT-2i users (0.20% vs 0.20%; HR 1.30; 95% CI, 1.11-1.52). Kaplan-Meier curves demonstrated consistent early separation favoring higher risk among GLP-1 RA users. Sensitivity analyses yielded similar patterns.

CONCLUSIONS: GLP-1 RA therapy was associated with a modest but statistically significant increased risk of NAION. While the absolute risk remains low, clinicians should consider ophthalmic risk assessment-particularly in patients with anatomical susceptibility or vascular risk factors-as GLP-1 RA use expands for diabetes and obesity management. Further mechanistic and prospective research is warranted.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Glucagon-like peptide-1 receptor agonists and the risk of nonarteritic anterior ischemic optic neuropathy: Evidence from a global real-world cohort

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief