Association of tirzepatide use with risk of osteoporosis compared with other GLP-1 receptor agonists: A retrospective cohort study using the TriNetX database.

AIMS: To determine whether tirzepatide use is associated with a higher risk of osteoporosis or fragility fractures compared with other glucagon-like peptide-1 receptor agonists (GLP-1 RAs). METHODS: In a retrospective cohort study using the TriNetX network, we identified 459,886 eligible patients with type 2 diabetes or obesity who initiated tirzepatide or other GLP-1 RAs between June 2022 and May 2024. We performed 1:1 propensity score matching to balance baseline characteristics. The primary outcome was a composite of new-onset osteoporosis or fragility fracture, assessed within a 14-month follow-up period. RESULTS: The matched study included 66,329 participants per group. Compared with other GLP-1 RAs, tirzepatide was associated with a higher risk of the primary outcome (hazard ratio [HR], 1.44; 95 % confidence interval [CI], 1.22-1.69) and of initiating osteoporosis therapy (HR, 1.61; 95 % CI, 1.22-2.12). Compared with the nonusers, tirzepatide users were associated with a significantly higher risk of the primary composite outcome of osteoporosis or fragility fracture (HR, 1.48; 95 % CI, 1.26-1.75) but not with other GLP-1 RAs (HR, 1.07; 95 % CI, 1.00-1.15). CONCLUSIONS: In this large real-world cohort study, initiation of tirzepatide was associated with a significantly higher risk of osteoporosis or fragility fractures compared to other GLP-1 RAs.