Concerns regarding potential ocular adverse events with glucagon-like peptide-1 receptor agonists (GLP-1RAs) have increased as the use of semaglutide expands worldwide. A systematic review and meta-analysis published in Graefe's Archive for Clinical and Experimental Ophthalmology evaluated the risk of nonarteritic anterior ischemic optic neuropathy (NAION) in adults with type 2 diabetes mellitus (T2DM) receiving semaglutide.

The analysis included 12 studies. Eight retrospective cohort studies involving 14,255,247 participants were included in the meta-analysis. The mean age was 59.3 ± 15.9 years, and 32.7% of participants were male. Outcomes were synthesized according to PRISMA guidelines and reported as pooled hazard ratios (HRs) with 95% confidence intervals (CIs).

Findings

• At 1-year follow-up, semaglutide use was associated with higher NAION risk compared with non-GLP-1RA therapy. The pooled HR was 3.36 (95% CI, 1.44-7.84; P < 0.001; I² = 97%).
• At 2-year follow-up, the pooled HR for NAION was 2.37 (95% CI, 1.46-3.85; P < 0.001; I² = 0%).
• Sensitivity analysis at 3 years showed a pooled HR of 2.37 (95% CI, 1.45-3.87; P < 0.001; I² = 28%).
• At 5-year follow-up, the pooled HR was 2.37 (95% CI, 0.62-3.92; P < 0.001; I² = 0%).

The analysis found that semaglutide use was associated with higher NAION risk in adults with T2DM compared with non-GLP-1RA therapy. The findings support continued evaluation of ocular safety outcomes during long-term GLP-1RA treatment.