Retatrutide works as a triple agonist, hitting GLP-1, GIP, and glucagon receptors all at once. Semaglutide only targets GLP-1, tirzepatide covers GLP-1 and GIP. That glucagon piece is the added ingredient unique to retatrutide, and it's mechanistically what drives the potential body composition perks. Sounds backwards at first, since glucagon is traditionally linked to muscle protein breakdown, and that link is genuinely one theoretical concern people raise about the medication.
Whatever muscle preservation edge retatrutide offers doesn't come from some direct anti-breakdown effect, it's more that the glucagon component reshapes how the body sources energy during a calorie deficit. With more energy available through fat burning and heat production, the body leans less on muscle tissue for fuel. How large that actual advantage is compared to the other two medications