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.
GLP-1 Therapies