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.