Glucagon receptor agonism and hepatic lipid oxidation — need advice

BethLabQueen said:

The pharmacokinetics explain nearly every practical question asked here.

I read this differently from BethLabQueen, on substance rather than tone. The objection nobody has made: this only works if the measurement is doing what we assume it is doing, and that assumption has not been tested here.

Ask again with the specifics and you will get a better answer than this one.

The figures, for anyone assembling their own picture. Numbers worth memorising for this class: Tmax one to three days for the weekly peptides, terminal half-life about a week for semaglutide and about five days for tirzepatide, steady state at four to five half-lives, subcutaneous bioavailability high enough that site choice is irrelevant.

TrialTracker_MD said:

The objection nobody has made: this only works if the measurement is doing what we assume it is doing, and that assumption has not been tested here.

Coming at TrialTracker_MD’s question from a different direction. The mechanism and the magnitude are separate questions. Agreeing that something happens says nothing about whether it happens enough to act on.

Following on from CryptoCarl — and this may be the naive question:

Which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working?

Closing the loop on my own question.

Update — tachyphylaxis to the gastric effect, persistence of the appetite effect. Two curves, and I had been watching the wrong one.