Longevity & AgingGLP-1 Drugs Shrink Fat but Also Muscle — New Strategies to Protect Lean Mass
The new generation of obesity drugs — semaglutide and tirzepatide — produce unprecedented weight loss of 15–21%, but a significant portion of that loss comes from lean mass, not just fat. Semaglutide sheds roughly 45% lean mass per unit of weight lost, versus 25% for tirzepatide. As these medications expand into older populations for cardiovascular, kidney, and sleep apnea indications, this lean-mass loss raises real concerns about frailty, falls, and fractures. This review evaluates strategies to counter the problem, including next-generation NuSH combinations targeting glucagon and amylin receptors, and myostatin-activin pathway inhibitors (MAPi) such as bimagrumab, which show early promise in selectively reducing fat while preserving or building muscle.
