Musculoskeletal Outcomes of Glucagon‐Like Peptide‐1 Receptor Agonists Versus Other Antiobesity Agents in Nondiabetic Adults

OBJECTIVE: This study aimed to evaluate the association of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with risks of osteoporosis, major osteoporotic fractures, and degenerative musculoskeletal disorders in nondiabetic adults with obesity compared with other obesity medications. METHODS: This retrospective cohort study included deidentified TriNetX data on ≥ 50-year-old nondiabetic adults with obesity. After 1:1 propensity score matching on demographic, clinical, and laboratory covariates, 18,062 GLP-1 RA users were compared with non-GLP-1 medication users. The primary outcome was incident osteoporosis; secondary outcomes included major osteoporotic fractures, cervical and thoracolumbar disc disorders, and osteoarthritis. RESULTS: GLP-1 RA use was associated with lower risks of osteoporosis (relative risk [RR] 0.48; 95% CI, 0.43-0.52; number needed to treat [NNT] = 28), major osteoporotic fractures (RR 0.15; 95% CI, 0.11-0.22; NNT = 88), cervical disc degeneration (RR 0.34; 95% CI, 0.28-0.41; NNT = 63), thoracolumbar disc disease (RR 0.36; 95% CI, 0.33-0.40; NNT = 20), and osteoarthritis (RR 0.45; 95% CI, 0.43-0.48; NNT = 9). Protective associations were consistent across age, sex, BMI, and drug subtype subgroups and remained robust in sensitivity analyses. CONCLUSIONS: GLP-1 RA use was associated with favorable musculoskeletal outcomes, including lower risks of osteoporosis and fractures, in nondiabetic adults with obesity compared with other obesity medications.