A large observational study published in JAMA Network Open has identified a potential association between the widely prescribed diabetes medications semaglutide and tirzepatide and an increased risk of certain optic nerve disorders, including nonarteritic anterior ischemic optic neuropathy (NAION), among adults with type 2 diabetes.

Semaglutide and tirzepatide belong to a class of drugs known as glucagon-like peptide-1 receptor agonists (GLP-1RAs). These medications have become foundational in the treatment of type 2 diabetes and obesity, offering benefits including improved blood sugar control, weight loss, and reduced cardiovascular risk. 

However, concerns have emerged from case reports and small studies suggesting that GLP-1RAs, particularly semaglutide, could be linked to rare, serious eye complications like NAION—a condition caused by insufficient blood flow to the optic nerve that can lead to sudden vision loss. 

To examine this potential risk on a large scale, researchers analyzed data from more than 118 million electronic health records across the United States, identifying over 1.5 million patients with type 2 diabetes who had no prior documented eye disorders. Using a method called target trial emulation, the team compared individuals prescribed semaglutide or tirzepatide against matched patients receiving other antidiabetic medications such as metformin, insulin, and first-generation GLP-1RAs. 

Key Findings

After matching patients by age, sex, and clinical characteristics, the researchers tracked outcomes over a 2-year follow-up period. They found:

• NAION incidence:

  • 35 patients (0.04%) in the semaglutide/tirzepatide group developed NAION

  • 19 patients (0.02%) in the comparison group developed NAION

  • This corresponded to a hazard ratio of 1.76, suggesting a 76% relative increase in risk, though the absolute risk remained very low

• Other optic nerve disorders:

  • 93 patients (0.12%) in the semaglutide/tirzepatide group had other optic nerve conditions

  • 54 patients (0.07%) in the comparison group experienced similar disorders, corresponding to a hazard ratio of 1.65

• No increased risk was seen for other visual pathway disorders, such as optic neuritis or papilledema

Although the absolute incidence of optic nerve disorders was low, the findings suggest that treatment with semaglutide or tirzepatide may modestly increase the risk of NAION and other optic nerve conditions compared with other antidiabetic therapies. 

According to the researchers, patients initiating or using semaglutide or tirzepatide—especially those with additional risk factors for optic nerve disease (e.g., older age, hypertension, sleep apnea, or vascular disease)—may benefit from regular ophthalmic evaluation and prompt reporting of visual symptoms. The authors call for prospective studies to confirm these associations, understand the underlying mechanisms, and determine whether specific patient subgroups are at higher risk.