Heart failure hospitalization reduction on semaglutide — 6 month update

PharmacoVig_BOS said:

Steady state is the thing most people miss.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.

The figures, for anyone assembling their own picture. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

NurseKim_ATL said:

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

There is a second half to this that has not been said yet. Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak. People who dose late are not losing a peak, they are letting the trough fall, and the appetite effect tracks the trough.

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

How much of the between-person variation is pharmacokinetic and how much is just adherence measured badly?

OP back with an update, since a thread like this is useless without one.

Update since I posted: I held at 1.7mg for a further twelve weeks and lost another 4kg slowly, which settles it for me. I was escalating because the number was available, not because I had stopped responding.