Semaglutide may raise risk for form of optic neuropathy in adults with type 2 diabetes
Key takeaways:
- Semaglutide was tied to nonarteritic anterior ischemic optic neuropathy (NAION) risk vs. nonuse in adults with type 2 diabetes.
- New semaglutide users did not have higher NAION risk vs. most other diabetes drugs.
Adults with type 2 diabetes may have a higher risk for developing nonarteritic anterior ischemic optic neuropathy while using semaglutide therapy than when they are not using the drug, according to findings from a retrospective study.
Prior studies have produced conflicting findings regarding the risk for nonarteritic anterior ischemic optic neuropathy (NAION), a form of optic neuropathy that could potentially cause blindness, while using semaglutide (Ozempic/Wegovy, Novo Nordisk). As Healio previously reported, data from Massachusetts Eye and Ear that was published in JAMA Ophthalmology in July found adults prescribed semaglutide for type 2 diabetes or obesity treatment were more likely to develop NAION than people taking non-GLP-1 medications. However, a retrospective analysis published in the Journal of Diabetes Science and Technology found GLP-1 receptor agonist use did not increase the risk for NAION compared with other non-GLP-1 drugs.
In a new study published in JAMA Ophthalmology that assessed data from 14 databases in the Observational Health Data Sciences and Informatics network, researchers also discovered mixed findings. Adults with type 2 diabetes using semaglutide had a higher NAION incidence rate than when they were not using the medication, but adults newly prescribed semaglutide did not have a significantly increased risk for NAION compared with most other diabetes medications in a second analysis.
“There are now several studies investigating the association between semaglutide and NAION, each with a different conclusion,” Cindy X. Cai, MD, MS, the Jonathan and Marcia Javitt Rising Professor and an assistant professor of ophthalmology at Wilmer Eye Institute at Johns Hopkins Medicine, told Healio. “We hoped to provide clarity around the association by conducting our study across 14 databases, two study designs and multiple sensitivity analyses.”
Adults with type 2 diabetes using semaglutide, dulaglutide (Trulicity, Eli Lilly), exenatide, empagliflozin (Jardiance, Boehringer Ingelheim), sitagliptin (Januvia, Merck) or glipizide from December 2017 through December 2023 were included. Researchers performed two analyses. The active-comparator analysis assessed NAION risk among new semaglutide users vs. adults using other medications. The self-controlled case-series analysis calculated NAION incidence rate ratios (IRR) during medication exposure compared with time adults were not using a medication. The researchers used two definitions of NAION. The sensitive definition defined NAION as one ischemic optic neuropathy diagnostic code, and the specific definition required an initial ischemic optic neuropathy diagnosis followed by a second diagnostic code within 90 days of the first one.
Risk for new semaglutide users
There were 166,932 adults included in the analysis, of whom 43,620 were new users of semaglutide. In the active-comparator analysis, adults initiating semaglutide had a similar NAION risk as those using dulaglutide (HR = 0.93; 95% CI, 0.46-1.91; P = .57), empagliflozin (HR = 1.44; 95% CI, 0.78-2.68; P = .12), sitagliptin (HR = 1.3; 95% CI, 0.56-3.01; P = .27) and glipizide (HR = 1.23; 95% CI, 0.66-2.28; P = .25) when the sensitive NAION definition was used. In an analysis using the specific NAION definition, new users of semaglutide had a higher NAION risk compared with empagliflozin users (HR = 2.27; 95% CI, 1.59-4.46; P = .02), but no other significant associations were observed.
Semaglutide use may raise NAION risk
In the self-controlled case-series analysis, semaglutide users were more likely to develop
P < .001) and specific definitions (IRR = 1.5; 95% CI, 1.26-1.79; P < .001). Those using exenatide also had a higher NAION risk compared with not using the medication, but only with the specific definition (IRR = 1.62; 95% CI, 1.02-2.58; P = .04). No other medications were associated with an increased risk for NAION in the case-series analysis.
“Semaglutide has a wealth of systemic benefits, but patients and prescribers of the medication should be aware of the association with an increased risk for NAION,” Cai said.
The researchers said some of the study limitations included a lack of data on patient risk factors and whether NAION risk is greater for patients with more severe diabetes. They also noted they could not determine whether risk differs for people with obesity.
Semaglutide use may raise NAION risk
In a related commentary, Joseph F. Rizzo III, MD, professor of ophthalmology and director of the neuro-ophthalmology service at Harvard Medical School and Massachusetts Eye and Ear in Boston, and Jimena Tatiana Hathaway, MD, MPH, ophthalmologist at the Harvard T.H. Chan School of Public Health, who were co-authors on the JAMA Ophthalmology study from July, wrote that although the research from Cai and colleagues found a lower NAION risk with semaglutide than what they observed in the Massachusetts Eye and Ear population, the findings should prompt health care professionals to make patients aware of the risk.
“In our opinion, based on our current knowledge, patients should not stop taking semaglutide on this account [of increased NAION risk] alone, especially given potential increases in morbidity from conditions that are well controlled by semaglutide, potential adverse effects of hyperglycemia caused by abrupt cessation of treatment and the seemingly low absolute risk of NAION,” Rizzo and Hathaway wrote. “However, it seems prudent to advise added caution for patients taking semaglutide or those who are considering starting this medication if they have experienced visual loss from any cause.”
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For more information:
Cindy X. Cai, MD, MS, can be reached at ccai6@jhmi.edu.
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