Semaglutide linked to modest increase in risk of nonarteritic anterior ischemic optic neuropathy

The use of semaglutide among individuals with type 2 diabetes (T2D) appears to carry a modest increase in the risk nonarteritic anterior ischemic optic neuropathy (NAION), according to a retrospective study.

For the study, researchers looked at 37.1 million individuals with T2D who were taking semaglutide, other glucagonlike peptide-1 receptor agonist (GLP-1RA; eg, dulaglutide and exenatide), or non–GLP-1RA medications (empagliflozin, sitagliptin, glipizide).

The association between semaglutide and NAION was assessed by employing an active-comparator cohort design (which compare new semaglutide users with those taking other GLP-1RAs and non–GLP-1RA drugs) and a self-controlled case-series (SCCS) analysis (which compared the participants’ risks during exposure and nonexposure periods for each drug).

Of the 43,620 new users of semaglutide in the Optum’s deidentified Clinformatics Data Mart Database, most were between 50 and 69 years of age (56 percent) and were female (61 percent). NAION occurred at a rate of 14.5 per 100,000 person-years among semaglutide users.

Using the sensitive NAION definition, the risk did not differ between new users of semaglutide and those taking non–GLP-1RAs (vs empagliflozin: hazard ratio [HR], 1.44, 95 percent confidence interval [CI], 0.78–2.68, p=0.12; vs sitagliptin: HR, 1.30, 95 percent CI, 0.56–3.01, p=0.27; vs glipizide: HR, 1.23, 95 percent CI, 0.66–2.28; p=0.25).

However, when the specific definition of NAION was used, a risk increase was observed among semaglutide users relative to empagliflozin users (HR, 2.27, 95 percent CI, 1.16–4.46; p=0.02).

Results of SCCS analysis indicated a positive association between semaglutide exposure and the risk of NAION (meta-analysis: incidence rate ratio, 1.32, 95 percent CI, 1.14–1.54; p<0.001).