Calories In Calories Out (CICO) doesn't explain obesity. You are dealing with biochemical machines (humans). CI enters this biochemical machine; here, the signal system should be effective to 'equalize'. Otherwise, you get all kinds of problems: obesity, t2d, cardiovascular events, etc.
These new generation of drugs (semaglutide, tirzapatide) deal with the signaling system (endocrine signaling, that is).
These new generation of drugs (semaglutide, tirzapatide) deal with the signaling system (endocrine signaling, that is).