GLP1Ra-based therapies and DXA-acquired musculoskeletal health outcomes: a focused meta-analysis of placebo-controlled trials

Objective: The objective of this study was to evaluate the effect of glucagon-like peptide-1 receptor agonist (GLP1Ra)-based therapies on change in dual-energy x-ray absorptiometry (DXA)-acquired lean mass (LM) or bone mineral density (BMD). Methods: PubMed and Web of Science were searched from database inception through January 29, 2024, for randomized, placebo-controlled trials reporting on change in DXA-acquired LM or BMD measures associated with 12+ weeks of GLP1Ra-based treatment. Of 2618 articles, 9 trials met prespecified search criteria, with 7 reporting on change in total body LM and 2 reporting on change in BMD. For LM outcomes, a hierarchical Bayesian model was used to estimate treatment mean differences. BMD outcomes were described narratively. Results: LM was reported in a total of 659 participants (GLP1Ra-based therapies: n = 419; placebo: n = 240), with follow-up times ranging from mean (SD) 12 to 72 (33.5) weeks. At baseline, participants were aged mean (SD) 41.7 (7.6) years, and 75% were female, with BMI values ranging from 30 to 43 kg/m². Compared with placebo, GLP1Ra-based treatment was associated with significantly reduced total body weight (−6.9 kg; 95% credible interval [CI]: −10.7 to −3.0). GLP1Ra-based treatment was also associated with significantly reduced LM (−1.9 kg; 95% CI: −3.5 to −0.2). Conclusions: Approximately 30% of body weight lost with GLP1Ra-based therapy is LM. More data are needed assessing BMD outcomes.