GLP-1s Linked With Increased Risk of Optic Nerve Disorders

Semaglutide or tirzepatide treatment among patients with diabetes was associated with an increased risk of optic nerve disorders, such as nonarteritic anterior ischemic optic neuropathy (NAION), according to a study published in JAMA Network Open.¹

“Glucagon-like peptide-1 receptor agonist (GLP-1RA) medications have transformed the treatment of type 2 diabetes (T2D) and obesity, with associated reductions in cardiovascular and nephrological complications,” wrote authors of the study. “Semaglutide and tirzepatide are second-generation GLP-1RA medications approved by the FDA for the treatment of diabetes and obesity.”

GLP-1s and their ability to transform diabetes care and obesity management have been increasingly noticeable as of late. According to a KFF Health tracking poll, at least 12% of US adults said they’ve taken a GLP-1RA at some point in time. For the sheer recognition of these medications amongst the public, 32% of US adults said they’ve heard “a lot” about GLP-1RAs, which is a 13% increase from 2023 to 2024.²

Using target trial emulation framework, researchers conducted their study to determine the causal effects of GLP-1s on outcomes of optic nerve disorders. | image credit: PhotoArtHub / stock.adobe.com

READ MORE: Initiation of Semaglutide Does Not Decrease Health Care Spending

Despite the notable rise in GLP-1 use in recent history, this drug class is often associated with adverse effects typically related to gastrointestinal outcomes, such as nausea, vomiting, diarrhea, gastroparesis, and constipation.^1,3 Recent studies, however, have shown associations between NAION and semaglutide use, leading to concerns of adverse outcomes among diabetes patients outside of the digestive system.

“Several retrospective studies from 2024 and 2025 reported a potential association of semaglutide with NAION in patients with diabetes and patients with obesity,” they continued.¹ “However, a meta-analysis of randomized clinical trials did not detect an association of GLP1-RA therapy, including semaglutide, with NAION.”

With conflicting evidence reported in the past few years, researchers wanted to better determine the association between NAION and GLP-1 use—namely semaglutide and tirzepatide. They hoped the significant reach of study participants within this new cohort would better inform pharmacist and provider decisions when counseling patients with diabetes, obesity, or a general need for GLP-1RAs.

“It remains unknown if semaglutide or tirzepatide is associated with other optic nerve and visual pathway disorders,” wrote the authors.¹ “This study leveraged a nationwide, multicenter database of electronic health records (EHRs) of more than 118 million US patients to conduct rigorous target trial emulation in patients with T2D to examine associations of semaglutide or tirzepatide with optic nerve and visual pathway disorders, including NAION.”

In this cohort study, researchers included EHR patient data from December 2017 to January 2023. Inclusion criteria called strictly for study participants with T2D, no previous diagnoses of eye disorders, and prescriptions for either semaglutide, tirzepatide, or another antidiabetic drug.

Using target trial emulation framework, researchers conducted their study to determine the causal effects of GLP-1s on outcomes like NAION.⁴ With this specific study design, they separated participants into 2 groups: those prescribed the GLP-1RAs semaglutide or tirzepatide and those prescribed alternative antidiabetic medications.¹

Among patients reporting use of semaglutide, tirzepatide, or other antidiabetic medications, the main outcomes researchers explored were any first-time diagnoses of disorders of optic nerve and visual pathways. Some of these disorders included optic neuritis, NAION, optic atrophy, and more.

The final analysis included a total of 159,398 patients, with an even split of 79,699 participants in the GLP-1RA group (mean age, 56.8 years; 51.7% women) and the other antidiabetic medications group (mean age, 56.2 years; 52.6% women).¹

Including all disorders explored in this study, the main associations between diabetes treatment and optic nerve disorders were only notable for NAION and “other” optic nerve disorders outside of those included in the study. However, among these associations, patients treated with semaglutide or tirzepatide were more likely to develop optic nerve disorders compared with patients on other antidiabetics.

Indeed, a total of 35 patients (0.04%) on semaglutide or tirzepatide reported NAION diagnoses compared with just 19 (0.02%) from the antidiabetic medication group. Furthermore, 93 participants (0.12%) reported other various optic nerve disorders compared with just 54 patients in the antidiabetic group.

“In a population of patients with T2D who had no prior diagnosis of eye diseases, this cohort study found that semaglutide or tirzepatide compared with other antidiabetic medications was associated with a differential risk of optic nerve and visual pathways, including increased risk of NAION and other optic nerve disorders, but not optic neuritis, papilledema, optic atrophy, or optic disc orders,” they continued.¹

With the overall risk of developing optic nerve disorder being minimal, the researchers findings are still significant enough to inform future use cases of any antidiabetic drug. Despite aligning with previous findings from 2024 and 2025, researchers believe further investigation is needed to replicate and confirm findings from the current study.

“Future studies are needed to replicate these findings, explore underlying mechanisms, identify individuals at increased risk for these potential complications, and examine other eye disorders,” concluded the authors.¹

READ MORE: Diabetes Resource Center

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References

1. Wang L, Volkow ND, Kaelber DC, Xu R. Semaglutide or tirzepatide and optic nerve and visual pathway disorders in type 2 diabetes. JAMA Netw Open. 2025;8(8):e2526327. doi:10.1001/jamanetworkopen.2025.26327

2. Montero A, Sparks G, Presiado M, et al. KFF Health tracking poll May 2024: the public’s use and views of GLP-1 drugs. KFF. May 10, 2024. Accessed August 12, 2025. https://www.kff.org/health-costs/poll-finding/kff-health-tracking-poll-may-2024-the-publics-use-and-views-of-glp-1-drugs/

3. Catanese L. GLP-1 diabetes and weight-loss drug side effects: “Ozempic face” and more. Harvard Health Publishing. February 5, 2024. Accessed August 12, 2025. https://www.health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more

4. Fu EL. Target trial emulation to improve causal inference from observational data: what, why, and how? J Am Soc Nephrol. 2023 Aug 1;34(8):1305-1314. doi: 10.1681/ASN.0000000000000152.