Dr.BariatricHTX said:

The mechanism is more central than most summaries suggest.

Pushing back on Dr.BariatricHTX here. The "earlier than weight loss explains" argument is weaker than this thread makes it sound. Blood pressure and inflammatory markers move fast and are downstream of early weight loss, so the mechanism is not as cleanly separable as the summaries imply.

Worth separating that from the pharmacology, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

One concrete data point for the thread. 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.

Dr.AddMedPHL said:

The "earlier than weight loss explains" argument is weaker than this thread makes it sound.

I'm 55 years old and want to share my perspective on cardiovascular risk as an older member of this community.

My doctor was initially hesitant because of my age, but the SELECT trial included patients up to 72 and showed consistent benefit across age groups. We started at the lowest dose with closer monitoring.

13 months later: down 60 lbs, off metoprolol, A1C from 8.0% to 5.5%. My cardiologist is thrilled. cardiovascular risk is absolutely relevant for older adults — don't let anyone tell you otherwise.

One thing that is still open after pam_columbus’s answer:

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.