Semaglutide Use Slightly Increase Optic Neuropathy Risk

Semaglutide use in patients with type 2 diabetes (T2D) slightly increases the risk of nonarteritic anterior ischemic optic neuropathy (NAION), research published in JAMA Ophthalmology shows. The study leveraged the Observational Health Data Sciences and Informatics (OHDSI) network — an international open-science collaborative centered around the Observational Medical Outcomes Partnership (OMOP) Common DataModel (CDM) — to investigate the association between semaglutide use and NAION.

The researchers found that use of the glucagonlike peptide-1 receptor agonist (GLP-1RA) semaglutide is linked with a more than 4 times greater risk of NAION compared with non-GLP-1RAs. Researchers in the current study further evaluated that tie by analyzing data in several databases, aiming to determine whether risk of NAION is greater with semaglutide, other GLP-1RA, or non-GLP-1RA weight loss medications (empagliflozin, sitagliptin, and glipizide).

Using active-comparator cohort design and self-controlled case-series (SCCS) analysis, the investigators reviewed data from December 2017 through 2023 of 37.1 million adults with type 2 diabetes (810,390 new semaglutide users) across 14 OHDSI databases. To meet the study’s sensitive definition’s criteria, patients needed 1 ischemic optic neuropathy diagnosis code. To acquire the specific definition’s criteria, the patient’s ischemic optic neuropathy diagnosis code had to be confirmed within 3 months.

The researchers discovered that the incidence rate of NAION for new semaglutide recipients was 14.5 per 100,000 person-years based on the sensitive definition and 8.7 per 100,000 person-years based on the specific definition. The investigators found that incidence proportions for NAION among new semaglutide recipients were 7.1 per 100,000 persons for the sensitive definition and 4.2 per 100,000 persons for the specific definition.

Based on the sensitive and specific definitions, NAION risk was similar for semaglutide use compared with use of dulaglutide or use of non-GLP-1RA medicines– with 1 exception: with the specific definition, NAION risk was 2.27 times greater for new recipients of semaglutide compared with empagliflozin recipients.

The self-controlled case-series analysis identified up to 39,104 patients with NAION based on the sensitive definition and 22,005 based on the specific definition. NAION incidence was greater with semaglutide exposure regardless of whether the researchers applied the sensitive or specific definition (sensitive incidence rate ratio [IRR], 1.32; specific IRR, 1.50). Exenatide was tied to a heightened incidence rate only with the specific definition (IRR, 1.62; P =.04). 

“In the OMOP CDM, drugs are identified by their active ingredients; the semaglutide group, therefore, included the subcutaneous injection (Ozempic [Novo Nor-disk]) and by-mouth formulation (Rybelsus [Novo Nordisk]),” the researchers explain. “The subcutaneous form of semaglutide has greater bioavailability, shows greater efficacy in glucose lowering, and is more commonly prescribed. Even with the inclusion of a less effective semaglutide formulation we were able to identify an increased risk of NAION.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Ophthalmology Advisor