Glucagon-Like Peptide-1 Receptor Agonists and the Risk of Thyroid Eye Disease

To evaluate whether glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with an altered risk of thyroid eye disease (TED) compared with other non-GLP-1RA glucose-lowering medications in patients with thyroid disease.

This retrospective, population-based cohort study utilized the TriNetX U.S. Collaborative Network to identify patients with thyroid disease initiating a GLP-1RA or a non-GLP-1RA active control medication. After 1:1 propensity score matching, 2 balanced cohorts of 173,618 patients each were analyzed. Matching variables included demographics, comorbidities, hemoglobin A1c, body mass index, concomitant diabetes medications, radioactive iodine therapy, thyroid-specific laboratory values, and diabetes complication severity. Outcomes included TED-related diagnoses, surgical interventions, and systemic steroid use. Time-to-event analyses were performed using Cox proportional hazards models.

GLP-1RA use was associated with a significantly lower risk of TED compared with the active control group. The risk of a composite TED-related diagnosis was lower at 1 year (hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.76-0.88), 2 years (HR 0.86; 95% CI, 0.81-0.91), and 3 years (HR 0.90; 95% CI, 0.86-0.95). Marked reductions were observed for TED-related surgical interventions (1-year HR 0.42, 95% CI 0.36-0.49; 3-year HR 0.54, 95% CI 0.48-0.61) and systemic steroid use. Subgroup analyses of patients with hyperthyroidism and individual agents demonstrated consistent protective associations.

In a large, rigorously matched cohort, GLP-1RA therapy was associated with a reduced risk of TED diagnoses, surgeries, and systemic steroid use compared to other glucose-lowering medications. These findings suggest a potential protective role for GLP-1 signaling in modulating orbital inflammation, though prospective trials are required for confirmation.