Glucagon-Like Peptide-1 Receptor Agonists and Risk of Uveitis.

Importance: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for glycemic control in diabetes, may possess anti-inflammatory properties. Understanding their potential protective role against uveitis could provide insights into novel therapeutic strategies.

Objective: To evaluate whether being prescribed a GLP-1RA is associated with a reduced risk of developing uveitis.

Design, Setting, And Participants: This was a retrospective cohort study using electronic health record (EHR) network data from 2006 to 2025. Propensity score matching was applied to control for demographics, smoking status, hypertension, body mass index, hemoglobin A1c, and diabetic retinopathy stage. Data from the US Collaborative Network of TriNetX, a large multicenter EHR platform, were used in this analysis. Included were patients with and without diabetes with prescriptions for GLP-1RAs, metformin, insulin, or sodium-glucose cotransporter 2 inhibitors (SGLT2is). The control groups consisted of patients without prescriptions for each medication.

Exposure: Use of GLP-1RAs, metformin, insulin, or SGLT2is, identified through prescription records.

Main Outcomes And Measures: The primary outcome was the incidence of noninfectious uveitis, identified using International Classification of Diseases (ICD) encounter diagnosis codes. Risk ratios (RRs) with 95% CIs were calculated to assess the association between GLP-1RA use and uveitis risk. Analyses included risk of overall uveitis and subtypes such as chorioretinal inflammation, anterior uveitis, panuveitis, and retinal vasculitis.

Results: A total of 516 052 patients were included in this study, 258 026 (mean [SD] age, 56.4 [13.7] years; 159 025 female [61.6%]) in the GLP-1RA group and 258 026 (mean [SD] age, 56.4 [14.0] years; 159 374 female [61.8%]) in the control group. The GLP-1RA cohort had a reduced risk of uveitis compared with controls (RR, 0.48; 95% CI, 0.46-0.51). 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). Compared with the cohorts taking metformin (RR, 0.58; 95% CI, 0.54-0.62) and insulin (RR, 0.57; 95% CI, 0.54-0.61), GLP-1RA prescriptions were associated with greater protection against uveitis. However, GLP-1RAs were associated with a slightly increased uveitis risk vs SGLT2is (RR, 1.17; 95% CI, 1.04-1.32). SGLT2i prescriptions were also associated with reduced uveitis risk compared with controls (RR, 0.52; 95% CI, 0.48-0.56).

Conclusions And Relevance: This cohort study found that GLP-1RA prescriptions were associated with a lower risk of uveitis compared with controls. These findings suggest potential anti-inflammatory benefits beyond glycemic control, warranting further investigation into their role in ocular inflammatory diseases.