A large real-world analysis has found a higher likelihood of osteoporosis or fragility fractures in individuals initiating tirzepatide compared with those starting other GLP-1 RAs. The investigation, published in Diabetes Research and Clinical Practice, evaluated bone-health outcomes using data from the TriNetX research network.
The cohort included 459 886 adults with type 2 diabetes or obesity who began tirzepatide or another GLP-1 RA between June 2022 and May 2024. After 1:1 propensity score matching, 66 329 participants remained in each group with well-balanced baseline characteristics. Over a 14-month follow-up, tirzepatide users had a higher risk of new-onset osteoporosis or fragility fracture (HR 1.44, 95% CI 1.22–1.69). The risk of initiating osteoporosis therapy was also elevated (HR 1.61, 95% CI 1.22–2.12).
When compared with nonusers, tirzepatide initiation was associated with a significantly higher risk of the composite outcome (HR 1.48, 95% CI 1.26–1.75). However, when compared exclusively with other GLP-1 RAs, risk differences were smaller (HR 1.07, 95% CI 1.00–1.15).
These findings indicate a measurable bone-health signal associated with tirzepatide use and support closer monitoring of skeletal risk, particularly among older adults and those with additional fracture risk factors.
