A monospecific drug, a drug that either raises or lowers a measurable, is difficult to make work. It cannot restore proper regulation and in an emergency it can be a real obstacle. A bispecific drug, one that ordinarily raises a measurable when it is too low and lowers the measurable when it is too high, is clearly preferred over the monospecific drug, and a trispecific drug that can also respond appropriately to an emergency situation would be still more preferred.
But that is just the tip of the iceberg. Consider how the body reads signals: as a rule, it is integrating various signals and checking for consistency. A pathway that was triggered by consistent signals is followed and does not reverse when there are inconsistent signals.
Imagine trying to create a drug that promotes autophagy in a person who is a complete stranger to fasting, a person who lives to eat, a gourmand, a person who never lets himself experience hunger.
The body reads multiple signals to determine when to step up the running of its autophagy programs. One is surely mTORC1 signaling, which is already integrating multiple signals and other is surely the absence of AMPK signaling. The former is integrating many signals indicating the abundance of energy and key nutrients and the latter is signaling the same by saying that just the opposite signal is absent. Any drug that is attempting to trigger an acceleration in autophagy in a chronically overfed person, where mTORC1 signaling is strong and AMPK signaling is non-existent, is going to run straight into a brick wall. If the monospecific drug works, it is going to have bizarre side effects. Most likely, it simply will not work. The body’s metabolism will remain the degenerative metabolism of the overfed state until fasting throws consistently opposite signals.