Semaglutide use significantly increases Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) risk in T2DM patients
Background
The global use of Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, has expanded dramatically for managing type 2 diabetes mellitus (T2DM). However, emerging pharmacovigilance data have raised concerns about a potential association between GLP-1RAs and Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION), a condition causing sudden vision loss due to impaired blood flow to the optic nerve. This meta-analysis aimed to clarify the risk of NAION in T2DM patients using semaglutide, addressing conflicting observational data.
Study Design
Researchers conducted a systematic review and meta-analysis, searching literature up to September 2025. They synthesized results following PRISMA guidelines, pooling data from twelve studies, which included eight retrospective cohorts for meta-analysis. The study population comprised 14,255,247 participants with type 2 diabetes mellitus, with a mean age of 59.3 ± 15.9 years and 32.7% males. The primary endpoint was the risk of NAION, evaluated by comparing patients using semaglutide to those on non-GLP-1RAs, presenting results as pooled Hazard Ratios (HR) with 95% confidence intervals (CI).
Results
The meta-analysis revealed a significantly increased risk of NAION in T2DM patients using semaglutide compared to non-GLP-1RAs. At 1-year follow-up, the pooled HR for NAION was 3.36 (95% CI: 1.44-7.84; p < 0.001; I² = 97%). This initial finding showed high heterogeneity. At 2-year follow-up, the pooled HR was 2.37 (95% CI: 1.46-3.85; p < 0.001; I² = 0%).
The 3-year risk, after sensitivity analysis, maintained a significant association with a pooled HR of 2.37 (95% CI: 1.45-3.87, p < 0.001;
I² = 28%). This association remained significant even at 5-year follow-up, with a pooled HR of 2.37 (95% CI: 0.62-3.92; p < 0.001;I² = 0%), indicating a persistent elevated risk over time.
Key Findings
- Semaglutide use increased NAION risk by a pooled HR of 3.36 (95% CI: 1.44-7.84) at 1-year in T2DM patients.
- The increased NAION risk persisted at 2-year follow-up with a pooled HR of 2.37 (95% CI: 1.46-3.85).
- A significant association remained at 3-year (HR 2.37, 95% CI: 1.45-3.87) and 5-year (HR 2.37, 95% CI: 0.62-3.92) follow-ups.
- All significant findings for NAION risk were associated with p < 0.001.
Why It Matters
This meta-analysis provides compelling evidence that semaglutide use is associated with an increased risk of NAION in T2DM patients, necessitating careful consideration in clinical practice. For peptide users and clinicians, this means a potential need for enhanced ophthalmic monitoring, especially in individuals with pre-existing risk factors for NAION. While semaglutide offers significant benefits for T2DM and weight management, this safety signal warrants discussion with patients about potential ocular adverse events. The findings suggest that this risk persists for at least 5 years, implying that long-term users should be aware of this potential complication. This information could influence prescribing patterns and patient counseling, particularly regarding the risk-benefit profile of GLP-1RAs.
semaglutide
naion
type 2 diabetes
meta-analysis
glp-1 agonist
ocular