G LP1Ra ‐based therapies and DXA ‐acquired musculoskeletal health outcomes: a focused meta‐analysis of placebo‐controlled trials

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Abstract 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/m 2 . 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.

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