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Obesity

Muscle mass loss during GLP1 receptor agonist therapy prevented with GDF8 and activin A blockade

Nature Reviews Endocrinology volume 21, page 458 (2025)Cite this article

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GLP1 receptor agonist therapies induce substantial weight loss, but up to 40% of this weight loss is lean mass, particularly muscle. Loss of muscle mass can be caused via activation of type II activin receptors ActRIIA and/or ActRIIB, and blockade of these receptors can lead to muscle growth in humans. A study in Nature Communications describes a strategy for preventing muscle mass loss during GLP1 receptor agonist therapy by dual blockade of the ActRIIA and ActRIIB ligands GDF8 (also known as myostatin) and activin A.

The researchers treated diet-induced obese mice with either a vehicle control, the GLP1 receptor agonist semaglutide alone, GDF8 and activin A antibody blockade alone (αMSTN–αActA) or semaglutide and αMSTN–αActA. The combination therapy of semaglutide and dual GDF8 and activin A blockade resulted in similar levels of total body weight loss to semaglutide alone, but statistically significantly greater protection from lean mass loss and substantially greater reduction in percentage fat mass than with semaglutide alone.

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References

Original article

  • Mastaitis, J. W. et al. GDF8 and activin A blockade protects against GLP-1–induced muscle loss while enhancing fat loss in obese male mice and non-human primates. Nat. Commun. 16, 4377 (2025)

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  1. Nature Reviews Endocrinology http://www.nature.com/nrendo/

    Olivia Tysoe

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  1. Olivia Tysoe
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Correspondence to Olivia Tysoe.

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Tysoe, O. Muscle mass loss during GLP1 receptor agonist therapy prevented with GDF8 and activin A blockade. Nat Rev Endocrinol 21, 458 (2025). https://doi.org/10.1038/s41574-025-01140-w

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