Muscle mass loss may represent a major concern with the use of SGLT2i, and different mechanisms may explain this effect: the reduction in insulin levels and increase in glucagon levels promoted by SGLT2 lead to the activation of gluconeogenesis, which might promote not only lipolysis in the adipose tissue, but also proteolysis in the skeletal muscle suppling amino acids to the liver and leading to sarcopenia [148]. Here, INS is linked to sarcopenia.