GLP-1 Receptor Agonists linked to modest reduction of risk of Femur Fracture: Study

A new study published in the journal of Bone that use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) was associated with a modest reduction in femur fracture risk. However, because the study was observational and may involve residual confounding and multiple testing, the findings are exploratory and require confirmation in prospective studies before being applied clinically.

People with T2DM face a well-known paradox in bone biology. Despite having normal or even elevated bone mineral density, the patients experience a higher risk of fractures, particularly in weight-bearing bones such as the hip and femur. GLP-1 RAs have attracted attention because of potential beneficial effects on bone metabolism.

This large retrospective cohort study used data from the TriNetX US Collaborative Network, which included analysis from over 3.6 million adults with T2DM identified between 2018 and 2022. Using a target trial emulation approach this study compared patients initiating GLP-1 receptor agonists with those starting dipeptidyl peptidase-4 inhibitors (DPP-4is).

The study initially identified 491,936 patients who began GLP-1 RA therapy and 345,484 who initiated DPP-4 inhibitors. To minimize bias and ensure comparable groups, this research applied propensity score matching, balancing baseline characteristics such as age, sex, and health status. After matching, each treatment cohort included 172,381 patients with a mean age of 59 years; 51% were men.

Participants were followed for up to 5 years, with an average follow-up period of approximately 40 months. During this time, the study monitored the occurrence of femur fractures. Statistical analysis using Cox proportional-hazards models revealed that patients taking GLP-1 receptor agonists experienced a significantly lower risk of femoral fractures when compared to those using DPP-4 inhibitors.

GLP-1 RA users had a 9% lower risk of femur fractures, with a hazard ratio of 0.91 and a 95% confidence interval ranging from 0.85 to 0.98. The protective association remained consistent across multiple sensitivity analyses designed to test the robustness of the results. Similar trends were also observed when GLP-1 RAs were compared to several other antidiabetic medications.

Since the study relied on observational data rather than a randomized clinical trial, unmeasured confounding factors may still influence the outcome. Also, the analysis involved multiple statistical comparisons, increasing the possibility that some associations may occur by chance. Overall, the study suggests that GLP-1 receptor agonists may offer a modest reduction in femur fracture risk among people with type 2 diabetes.

Reference:

Chang, Y. J., Fuh, C. S., Chang, J. F., Chen, M. T., & Tsai, M. H. (2026). Association between glucagon-like peptide-1 receptor agonists and femur fracture risk in type 2 diabetes: A large-scale target trial emulation. Bone, 207, 117851. https://doi.org/10.1016/j.bone.2026.117851