Skeletal effects of GLP-1 receptor agonist therapy in adults with overweight or obesity: a systematic review.

In 30 seconds

This systematic review examined randomized evidence on bone mineral density (BMD) and bone-turnover markers in adults with overweight or obesity receiving GLP-1 receptor agonists. Eight randomized controlled trials (493 participants) were included; results were reported separately by agent, with no meta-analysis because agents and their weight-lowering effects differed. Findings varied across agents and trials. In the single semaglutide trial, treatment was associated with lower lumbar-spine BMD (estimated treatment difference −0.018 g/cm²; p = 0.007), lower whole-body BMD, and higher CTX. The authors judged evidence very low certainty and insufficient to establish skeletal effects.

Key findings

• Eight randomized trials included 493 participants; certainty of evidence was very low for every GLP-1 receptor agonist.
• In the semaglutide trial, lumbar-spine BMD was lower (ETD −0.018 g/cm², p = 0.007) and CTX was higher (MD 166.50 pg/mL; 95% CI 66.60 to 266.40).
• Liraglutide 3.0 mg daily was associated with lower lumbar-spine and total-hip BMD, whereas at 1.8 mg daily no BMD site changed materially.
• Exenatide findings were inconsistent, with lumbar-spine BMD estimates ranging from 0.03 g/cm² (95% CI 0.02 to 0.03) to −0.04 g/cm² (95% CI −0.15 to 0.07).

Why it matters

GLP-1 receptor agonists are used for weight management, but weight loss and skeletal outcomes may be relevant together when considering bone health. This review highlights that available randomized data do not yet clarify whether effects on BMD or bone turnover differ by agent, dose, or population. The uncertainty is important when interpreting skeletal safety, rather than evidence of a settled class effect.

What to keep in mind

Evidence was sparse and clinically heterogeneous, with no agent supported by more than one trial at low risk of bias. The review did not pool results, and certainty was very low for every agent.