Tirzepatide Use Is Associated with Reduced Risk of Carpal Tunnel Syndrome in Overweight and Obese Adults.

This study aimed to evaluate the association between tirzepatide use and the risk of carpal tunnel syndrome (CTS) and CTS surgery compared with both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and other anti-obesity medications in individuals who are overweight or obese. We conducted a multicenter retrospective cohort study using the TriNetX US Collaborative Network with a target trial emulation design. Adults aged ≥ 18 years who are overweight or obese and initiated tirzepatide, GLP-1RAs, or other anti-obesity medications (including orlistat or phentermine) between January 2022 and December 2024 were included. Propensity score matching (1:1) was applied to balance demographics, BMI, comorbidities, and socioeconomic variables. Primary outcomes were incident CTS and CTS surgery, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated. Sensitivity analyses varied lag periods, follow-up durations, analytical frameworks, and matching strategies, while subgroup analyses examined age, sex, race, BMI, and diabetes status. The study complied with the Declaration of Helsinki and received IRB exemption (#11312-E01 and #11212-E02). After matching, well-balanced cohorts were achieved across comparisons. Tirzepatide use was associated with a significantly lower risk of CTS compared with GLP-1RAs (HR 0.82; 95% CI 0.71-0.95), with no significant difference in CTS surgery. In comparison with other anti-obesity medications, tirzepatide was associated with reduced risks of both CTS (HR 0.75; 95% CI 0.65-0.85) and CTS surgery (HR 0.64; 95% CI 0.44-0.94). In conclusion, Tirzepatide use was associated with reduced risks of CTS, particularly when compared with non-GLP-1RA therapies, suggesting potential metabolic and neuroprotective benefits.