The review says that tirzepatide and similar incretin drugs, which are already used for weight loss and diabetes, might also help keep muscle healthy. In animal studies they seem to reduce muscle wasting, improve muscle cell growth, boost mitochondria, and lower fat inside muscles. Human data are still limited, but the drugs appear to cause a proportional loss of fat and lean mass, suggesting they don’t dramatically shrink muscle when you lose weight.

Skeletal muscle is the largest insulin-sensitive tissue in the human body, playing a crucial role in glucose homeostasis, body mobility and overall metabolic health. In obesity and type 2 diabetes (T2D), skeletal muscle undergoes structural, functional, and metabolic alterations, including reduced muscle mass, impaired contractile function, increased myosteatosis, mitochondrial dysfunction, and chronic low-grade inflammation. Incretin-based therapies such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) RAs are highly effective treatments for T2D and obesity, producing substantial weight loss. While clinical trials suggest proportional loss of fat and lean mass when using incretin-based therapies, emerging preclinical and translational data indicate potential muscle-specific beneficial effects such as attenuation of atrophy, improved myogenesis, enhanced mitochondrial function and reduced myosteatosis. This review comprehensively summarizes the current preclinical and clinical evidence on the impact of incretin-based therapies on skeletal muscle mass, composition, metabolism, and performance, focusing on mechanistic insights from animal models and translational findings from human studies.