GLP-1RAs associated with reduction in uveitis development risk in new study

The study used the US Collaborative Network in the TriNetX, which holds EHR data of over 120 million patients from 60 health care organizations spanning from 2006 to 2025. Image credit: AdobeStock/DavidElkins

A recent study published in JAMA Ophthalmology found that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were associated with a reduction in the risk of developing uveitis. These findings support the potential anti-inflammatory benefits of the drug class and add to the growing body of literature that suggests that GLP-1RAs could decrease incidence of ophthalmic diseases.¹

“Understanding the protective effects of GLP-1RAs may have important implications for the management of both metabolic and inflammatory diseases, including uveitis,” the study authors, led by Nitesh Mohan, BS, of Cole Eye Institute, Cleveland Clinic, Case Western Reserve University, and Cleveland Clinic Lerner College of Medicine, in Cleveland, Ohio, stated.

Researchers noted that while recent studies have shown that GLP-1RAs may decrease the risk of degenerative diseases such as age-related macular degeneration (AMD) and glaucoma, investigation into whether the drug class can influence the risk of inflammatory eye diseases is largely lacking research. They also stated that AMD and glaucoma to have inflammatory components that contribute to disease progression.¹

The study used the US Collaborative Network in the TriNetX, which holds EHR data of over 120 million patients from 60 health care organizations spanning from 2006 to 2025. The study authors created 4 different cohorts of patients prescribed GLP-1RA from a total of 516,052 patients included in the study, consisting of an overall cohort, a cohort with diabetes, a cohort with type 2 diabetes, and a cohort without diabetes. Additionally, patients with a prescription for GLP-1RA listed in their medical record were included in the treatment group. Another 3 subgroups for the control cohort with diabetes were created in order to assess patients with diabetes taking metformin, insulin, and SGLT2is in order to compare uveitis risk with the medications with GLP-1RAs. Incidence of new-onset noninfectious uveitis was assessed by using 4 different outcome groups: chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis.¹

First, the primary analysis assessed the risk of uveitis any time after the first GLP-1RA prescription via 2 sensitivity analyses. Outcomes were restricted to uveitis diagnoses occurring within 1 year, 3 years, and 5 years of this first prescriptions. An analysis was then performed on only patients receiving monotherapy, excluding individuals using other major antihyperglycemic classes.¹

“In the overall group, patients prescribed GLP-1RAs had a 51.7% relative reduction in risk of developing a new diagnosis of uveitis (RR, 0.48; 95% CI, 0.46-0.51; P < .001),” the study authors stated. “This was consistent among those with type 2 diabetes (RR, 0.54; 95% CI, 0.51-0.58) and those without diabetes (RR, 0.52; 95% CI, 0.46-0.59). This trend remained consistent across all comparisons, with patients prescribed GLP-1RAs exhibiting roughly half the risk of developing uveitis (including all subtypes) compared with those not prescribed a GLP-1RA.”

The results were also confirmed in the secondary analysis observing outcomes of uveitis occurring within 1 year, 3 years, and 5 years of medication initiation.¹ “This protective outcome was consistent across different subtypes of uveitis and in subgroup analyses, with both patients with and without diabetes who were prescribed GLP-1RAs experiencing a lower risk of new uveitis diagnoses,” the study authors stated.

Researchers noted limitations of the study include the usage of aggregated, deidentified EHR data, mostly relating to the reliance on ICD-10, RxNorm, and CPT coding and the assumption that all patients undergoing diagnoses, medication prescriptions, and procedures have been accurately coded by physicians, “which may not necessarily be the case.” The retrospective, observational study may also not indicate causality and requires further investigation through additional studies before they can be used to inform prescribing practices or aid in medication selection, the researchers added.¹

Reference:

1. Mohan N, Srivastava SK, Schulgit MJ, Nowacki AS, Kaelber DC, Sharma S. Glucagon-like peptide-1 receptor agonists and risk of uveitis. JAMA Ophthalmol. 2025. doi:10.1001/jamaophthalmol.2025.2822