Obesity affects over 1 billion people worldwide and is linked to more than 230 health complications, with cardiovascular disease being a leading cause of mortality. Losing 5%-10% of body weight is considered clinically significant for improving health. This weight loss can be achieved through pharmacotherapy, including glucagon-like peptide 1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic peptide dual receptor agonists, and GLP-1/glucose-dependent insulinotropic peptide/glucagon triple receptor agonists (such as semaglutide, tirzepatide, and retatrutide, respectively). While much of the weight loss comes from fat mass, these treatments also result in the loss of lean mass, including muscle. This loss of muscle may contribute to difficulties in maintaining weight over the long term and can lead to sarcopenia. Therefore, the focus of new anti-obesity treatments should be primarily on reducing fat mass while minimizing the loss of muscle mass, ideally promoting muscle gain. Research focusing on human myocytes has identified more than 600 myokines associated with muscle contraction, which may play a crucial role in preserving both muscle mass and function. We explored the potential of new anti-obesity agents and their combinations with incretin-based therapies to achieve these outcomes. Further studies are needed to better understand the functional implications of lean mass expansion during weight loss and weight maintenance programs.
