Diabetes research and clinical practiceNov 11, 2025

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

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 1, 2026

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).

Simplified

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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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

PubMed

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

Abstract

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