A network meta-analysis published in Diabetes, Obesity & Metabolism compared the risk of nonarteritic anterior ischemic optic neuropathy across individual GLP-1 receptor agonists, and reported that the risk was not the same for every drug in the class.

Nonarteritic anterior ischemic optic neuropathy, or NAION, is sudden vision loss caused by impaired blood flow to the optic nerve head. GLP-1 receptor agonists, the class that includes semaglutide and liraglutide, are widely prescribed for type 2 diabetes and obesity, and the authors describe the link to NAION as emerging evidence rather than settled.

Which agent carried the strongest signal

Compared with non-GLP-1RA treatments, semaglutide showed the highest risk in the meta-analysis, with a hazard ratio of 1.538 (95% CI: 1.305 to 1.816). Liraglutide followed at 1.251 (95% CI: 1.080 to 1.450).

The authors then went to the FDA Adverse Event Reporting System for validation. Semaglutide produced a strong disproportionate reporting signal there (ROR = 94.534, 95% CI: 83.093 to 107.552), while liraglutide's signal was statistically significant but far weaker (ROR = 4.519, 95% CI: 2.617 to 7.802).

Why that huge FAERS number is not a rate

A reporting odds ratio near 95 looks alarming next to a hazard ratio of 1.5, and the gap is worth understanding. Disproportionality measures how often an event shows up in a voluntary reporting database relative to everything else in it, which means heavy media attention on one drug can inflate it without telling you anything about incidence.

CASP3 and the docking work

Network toxicology identified CASP3 as the central hub target, and pathway enrichment pointed mainly to Alzheimer's disease, neurodegeneration, and lipid and atherosclerosis pathways. Molecular docking suggested both semaglutide and liraglutide had high binding affinity to CASP3.

Limitations

The mechanistic half of this paper is computational. Network toxicology and docking generate hypotheses about targets and binding, not evidence of what happens in an optic nerve, and no experimental confirmation is reported here.

The pharmacovigilance half inherits the usual problems of spontaneous reporting: no denominator, no control over who reports, and no way to establish causation. The authors frame the whole exercise as providing insights into possible risk differences that may guide future research.

Where the eye question goes next

What this adds is a ranking within the class, which is more specific than most GLP-1 eye coverage has managed. What it does not settle is whether the drugs cause NAION at all, or why semaglutide sits at the top.