The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation

Incretin receptor agonists can achieve up to 15-25% weight loss in many patients, similar to bariatric surgery.

• Over 25% of weight lost from both surgery and medication typically comes from fat-free mass, including muscle.
• Loss of muscle and bone, as well as anemia, can negatively impact physical function and overall health, especially in older adults.
• The myostatin-activin-follistatin-inhibin system is important for maintaining muscle and bone during weight loss.
• Activins and myostatin promote muscle loss, while follistatins help preserve lean mass during negative energy balance.
• Novel compounds that inhibit activin and myostatin signaling may prevent muscle loss and promote fat loss.
• A combination of these new medications with incretin receptor agonists could improve body composition and metabolic health during weight loss.

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