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.