SURMOUNT-5: Tirzepatide vs semaglutide head-to-head — looking for input

chris_chi24 said:

Dose-response modeling for tirzepatide: Emax model fitting to the STEP/SURMOUNT dose-finding data shows: Semaglutide: ED50 ≈ 0.6mg, Emax ≈ -18%, Hill…

All true, with one condition: that curve is for people who reached the dose on schedule. Anyone who slowed the ladder for tolerability is on a different, flatter curve, and comparing yourself with the published mean will make you feel like a non-responder when you are not.

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

RetaRick_CA said:

All true, with one condition: that curve is for people who reached the dose on schedule.

Agreed, though "tolerable" needs defining. A dose you tolerate by eating almost nothing is not tolerated, it is being paid for somewhere else — usually in lean mass, sometimes in adherence three months later.

RetaRick_CA said:

All true, with one condition: that curve is for people who reached the dose on schedule.

There is a second half to this that has not been said yet. The dose-response is real but shallow at the top. Across STEP 1 and STEP 4 the gap between 1.7mg and 2.4mg is a couple of percentage points of body weight on average, and the average is carrying a wide spread — plenty of people at 1.7mg sit above the 2.4mg mean. If a dose is working and tolerable, "working" is the relevant variable, not "maximal".

Adding the numbers, since they settle part of this. 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.

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. No action needed from anybody.