Abstract

Objective: To evaluate whether semaglutide use is associated with thyroid eye disease (TED)-related outcomes among patients with autoimmune thyroiditis and type II diabetes mellitus (T2DM).

Methods: Adults with thyrotoxicosis (International Classification of Diseases [ICD-10]: E05) and T2DM were identified from the TriNetX US Collaborative Network. T2DM was defined by ICD-10 (E11) or laboratory criteria. The exposed cohort included individuals prescribed semaglutide on or after its Foood and Drug Administration approval (December 5, 2017). The control cohort included patients treated with non-glucogon-like peptide-1 receptor agonist antihyperglycemic agents without prior glucagon-like peptide-1 receptor agonist exposure. Propensity score matching (1:1) was performed using demographics, comorbidities, medications, and health care utilization variables. Five-year outcomes included: (1) TED-related diagnoses; (2) systemic corticosteroid use; (3) TED-related surgical interventions; (4) radiation treatment; and (5) teprotumumab use. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated.

Results: After matching, 23,279 patients were included per group (mean age: 60.1 years; 75% female). At 5-year, semaglutide users had lower rates of TED-related diagnoses (2.16% vs 2.82%; RR: 0.76; 95% CI: 0.68-0.86), systemic corticosteroid use (22.71% vs 26.39%; RR: 0.86; 95% CI: 0.82-0.90), TED-related surgical interventions (0.30% vs 0.42%; RR: 0.70; 95% CI: 0.51-0.96), and radiation treatment (1.17% vs 2.05%; RR: 0.57; 95% CI: 0.49-0.67). Teprotumumab use was rare and similar between groups (0.08% vs 0.08%; RR: 1.00; 95% CI: 0.52-1.92).

Conclusions: Semaglutide use was associated with fewer TED-related diagnoses and treatments over 5 years, supporting a potential protective role. Further studies are warranted to confirm these associations and clarify underlying mechanisms.