GLP-1 RAs Linked to Lower Fragility-Fracture Risk

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) initiation was associated with a lower 3-year risk of fragility fracture than dipeptidyl peptidase-4 inhibitor initiation among adults aged 50 to 90 years with type 2 diabetes, according to a comparative-effectiveness study published in JAMA Network Open.

Investigators emulated a target trial using deidentified US electronic health records from the TriNetX Research Network. The analysis included 133,606 adults with type 2 diabetes who newly initiated a GLP-1 RA or dipeptidyl peptidase-4 inhibitor from 2015 through 2022 and had no fragility fracture during the preceding year.

GLP-1 RA initiation was associated with a statistically significant 21% lower 3-year fragility-fracture risk than the active comparator. The association was most apparent for vertebral and hip or femur fractures and persisted after adjustment for baseline clinical characteristics and use of other glucose-lowering medications.

Analyses suggested that the association was independent of changes in body mass index and hemoglobin A1c. A sensitivity analysis among people without type 2 diabetes did not show a reduced fracture risk. The association also attenuated by the third year, leaving uncertainty about its durability with longer treatment exposure.

The study used observational health-record data, so residual confounding and differences in treatment selection remain possible despite target-trial methods and propensity adjustment. The investigators said prospective studies are needed to establish causality and define the duration, magnitude, and biological mechanisms of the association and the long-term skeletal effects of GLP-1 RAs.

Source: Hamad CD, Wiener J, Golzar A, et al. Glucagon-like peptide-1 receptor agonists and fragility fracture risk in type 2 diabetes. JAMA Netw Open. 2026;9(7):e2625141. doi:10.1001/jamanetworkopen.2026.25141.