While a single-center study published this past July observed an association between semaglutide and an increased risk of NAION, a recent larger, real-world study failed to find a link between the two. Photo: Novo Nordisk. Click image to enlarge.

A study published over the summer by Hathaway et al. revealed a link between semaglutide—a popular glucagon-like peptide 1 receptor agonist (GLP-1RA) used to treat type 2 diabetes and obesity—and an increased risk of non-arteritic anterior ischemic optic neuropathy (NAION). Since that analysis recruited participants from a single neuro-ophthalmology practice (Massachusetts Eye and Ear in Boston), a separate team of researchers questioned whether these findings apply to broader populations. To investigate, they conducted a population-based real-world study on data from 200 million people across 21 countries within the TriNetX global network to assess whether semaglutide users possess a higher risk of NAION.

The final analysis included Caucasian individuals older than 18 with type 2 diabetes mellitus (T2DM) or obesity, who were further divided into one of three groups for comparison: T2DM-only (n=37,245), obesity-only (n=138,391) and T2DM with obesity (n=64,989). Baseline characteristics, such as age, sex, BMI, hemoglobin A1c, comorbid conditions and medications, were balanced between groups. The researchers then compared the effects of semaglutide with those of various non-GLP-1RA glucose-lowering or weight-loss medications.

The results demonstrated that semaglutide use did not increase the risk of NAION development among the general population compared with non-GLP-1RA drugs. This finding was consistent among the T2DM-only group, the obesity-only group and the T2DM with obesity group at one, two and three years of follow-up.

“Our findings contrast with those of Hathaway et al. probably because of the differences in the study populations and designs,” the study authors explained in their paper for Ophthalmology. They noted that while the prior study “involved patients referred to a single major medical center in a city with a high degree of medical sophistication, our study included individuals from a more general clinical setting.” Additionally, they pointed out that “differences in population characteristics and drug prescription preferences between single institutions and global databases may contribute to varying results,” as can differences in healthcare systems across regions and countries.

Considering these findings observed across a large, real-world cohort, the researchers concluded that “avoidance of semaglutide based solely on concerns regarding the risk of NAION may not be warranted, as its potential benefits for blood glucose control and cardiovascular health likely outweigh its potential risks.”