Female Mice Protected from Semaglutide-Induced Muscle Loss During Weight Loss

The GLP-1 receptor agonist semaglutide is highly effective for weight management and type 2 diabetes, leading to significant reductions in body weight. However, a common concern with rapid weight loss, particularly with GLP-1 agonists, is the concomitant loss of lean muscle mass, which can negatively impact strength, metabolism, and overall health. While the efficacy of semaglutide is well-established, sex-specific differences in its impact on muscle preservation during weight loss remain poorly understood.

The study revealed significant sex-dependent differences in muscle preservation. Both male and female mice treated with semaglutide experienced comparable total body weight loss, averaging 18% from baseline. However, the composition of this weight loss varied dramatically between sexes. Male mice exhibited a substantial 15% reduction in lean muscle mass, whereas female mice experienced a significantly smaller 5% decrease in lean mass. This indicates a 3-fold greater protection against muscle loss in females. Furthermore, markers of muscle protein synthesis were 30% lower in semaglutide-treated male mice compared to controls, while female mice showed only a 10% reduction, suggesting a preserved anabolic state. The most significant finding was that female mice maintained significantly higher lean muscle mass compared to males despite similar overall weight loss, showing a p<0.01 difference in muscle preservation and a p<0.005 difference in muscle protein synthesis rates.