The present invention relates to compositions and methods for altering body composition in a subject, wherein the alteration of body composition is an increase in muscle mass and a reduction of fat mass simultaneously. The present invention also relates to compositions and methods for reducing fat mass in a subject. The compositions and methods also increase muscle volume and lean body mass in the subject. The present invention also relates to compositions that comprise a GDF8 inhibitor and an Activin A inhibitor and the use of such compositions to treat diseases and disorders characterized by increased fat mass, and/or decreased muscle volume.