Semaglutide reduces skeletal muscle mass by approximately 15–20% in obese mice without impairing maximal isometric muscle strength under steady-state conditions, indicating a dissociation between muscle size and functional capacity during pharmacologically induced weight loss.

When semaglutide reduces food intake, the body enters a low-energy state that makes muscle stem cells pause their growth and repair work. This causes muscles to shrink over time. However, the existing muscle fibers become more efficient at using energy, so they can still generate full strength even though they are smaller. The muscle does not lose its ability to contract forcefully because the remaining fibers adapt to maintain performance without needing more size.