Background: Type 2 diabetes and obesity rates are expected to rise, possibly increasing the usage of Glucagon-like peptide-1 (GLP-1) agonists. Use of these agents for nondiabetic patients for weight loss I s approaching the number prescribed for diabetes. GLP-1 agonists may influence bone metabolism by promoting formation and reducing resorption, but their impact on fracture risk remains unclear. While some studies show no association, others suggest increased vulnerability. Most prior research has examined overall fracture risk without considering specific skeletal sites. This study aimed to compare site-specific fracture rates in adults with T2DM or obesity receiving GLP-1 therapy with those who do not receive GLP-1.
Methods: This is a retrospective cohort study that was conducted using the TriNetX Research Network. The study included patients aged 18 to 90 who were diagnosed with type 2 diabetes or obesity between January 1, 2010, and July 26, 2025. Fracture rates at different anatomical sites were analyzed within the 1-month to 5-years range after diagnosis.
Results: There was no significant difference in the rates of spine and lower leg/ankle fractures. Patients who took GLP-1 agonists had significantly lower rate of nonunion (RR 0.793), forearm fractures (RR 0.952), femur fractures (RR 0.79), and pelvis fractures (RR 0.884). Patients who received GLP-1 therapy had significantly higher rates of fracture in shoulder and upper arm (RR 1.105), rib fracture (RR 1.101), wrist/hand (RR 1.215) and foot/toe fractures (RR 1.425).
Conclusions: These findings suggest that association between GLP-1 use and fracture risk may vary by anatomical site and needs further investigation with prospective, randomized studies.