The interplay of GLP‐1 receptor agonist use, chronic kidney disease and fracture risk in obese pAtients: a retrospective cohort study

Aims To evaluate the association between Glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) use and fracture risk in patients with or without chronic kidney disease (CKD). Methods A retrospective cohort study was conducted using TriNetX, including patients aged 18–50. Two primary cohorts were defined: obese patients with CKD on GLP‐1RAs ≥ 1 year (CKD+/GLP‐1RA+) and obese patients with CKD not on GLP‐1RAs (CKD+/GLP‐1RA‐). A subgroup analysis compared CKD+/GLP‐1RA + patients to obese patients without CKD on GLP‐1RAs (CKD‐/GLP‐1RA+). Primary outcomes were upper and lower limb fractures. Risk analysis and Kaplan–Meier survival analysis assessed fracture incidence over 5 years. Results After matching, 13 441 patients were included per cohort. CKD+/GLP‐1RA + patients had fewer fractures than CKD+/GLP‐1RA‐ patients (Risk Difference: ‐0.016, 95% CI: −0.018, −0.013; RR: 0.196, 95% CI: 0.145, 0.265; OR: 0.193, 95% CI: 0.143, 0.261), with higher fracture‐free survival (99.31% vs . 95.47%; p < 0.001). Subgroup analysis (13 723 patients per cohort) showed CKD+/GLP‐1RA + patients had a slightly higher fracture risk than CKD‐/GLP‐1RA + patients (Risk Difference: 0.003, 95% Cl: 0.001, 0.004; RR: 2.357, 95% Cl: 1.516, 3.665; OR: 2.364, 95% Cl: 1.518, 3.680), with lower fracture‐free survival (98.87% vs . 99.19%; p < 0.001). Conclusion These findings suggest a possible CKD‐associated modification on the skeletal effects of GLP‐1RAs, implicating that CKD patients' bone health should be monitored during GLP‐1RA treatment.