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

Nov 11, 2025Diabetes research and clinical practice

Tirzepatide use may be linked to osteoporosis risk compared to other GLP-1 receptor drugs

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Abstract

Tirzepatide use is associated with a 44% higher risk of osteoporosis or fragility fractures compared to other glucagon-like peptide-1 receptor agonists.

In a cohort of 66,329 matched participants, tirzepatide users had a hazard ratio of 1.44 for developing osteoporosis or fragility fractures compared to those using other GLP-1 RAs.
The risk of initiating osteoporosis therapy was 61% higher for tirzepatide users (HR, 1.61) than those using other GLP-1 RAs.
Tirzepatide users were also associated with a 48% higher risk of the primary composite outcome when compared to nonusers.
No significant difference in risk for osteoporosis or fragility fractures was observed between users of tirzepatide and other GLP-1 RAs (HR, 1.07).

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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.

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

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