The Risk of Vestibular Disorders with Semaglutide and Tirzepatide: Findings from a Large Real-World Cohort

<b>Background/Objectives</b>: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have revolutionized the treatment of type 2 diabetes and obesity. While their metabolic benefits are well-established, their potential effects on vestibular function remain unexplored. This study investigated the association between GLP-1RA use and the risk of vestibular disorders. <b>Methods</b>: Using the TriNetX research network (accessed 3 November 2024), we conducted a retrospective cohort study of adults prescribed semaglutide (<i>n</i> = 419,497) or tirzepatide (<i>n</i> = 77,259) between January 2018 and October 2024. Cases were matched 1:1 with controls using propensity scores based on demographics and comorbidities. The primary outcome was new-onset vestibular disorders, analyzed at 6 months, 1 year, and 3 years after treatment initiation. <b>Results</b>: Both medications were associated with an increased risk of vestibular disorders. Semaglutide users showed a higher cumulative incidence (0.12% at 6 months to 0.41% at 3 years) compared to controls (0.03% to 0.16%, <i>p</i> < 0.001), with hazard ratios ranging from 4.02 (95% CI: 3.33-4.86) at 6 months to 4.95 (95% CI: 4.51-5.43) at 3 years. Tirzepatide users demonstrated similar patterns but lower absolute rates (0.10% at 6 months to 0.19% at 3 years vs. controls 0.04% to 0.15%), with hazard ratios from 3.19 (95% CI: 2.11-4.81) to 4.55 (95% CI: 3.43-6.03). The direct comparison showed a higher risk with semaglutide versus tirzepatide (RR 1.53-2.04, <i>p</i> < 0.001). <b>Conclusions</b>: GLP-1RA therapy is associated with an increased risk of vestibular disorders, with a higher risk observed with semaglutide compared to tirzepatide. These findings suggest the need for vestibular symptom monitoring in patients receiving these medications and warrant further investigation into underlying mechanisms.