Writing this once so I can stop repeating it across threads. It is about semaglutide, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
Steady state is the thing most people miss. The terminal half-life is about a week, so every dose step takes four to five weeks to fully express itself. Judging a step at day ten is judging the ascent, not the plateau, and it is the single commonest reason people escalate before they needed to.
The condition it depends on
"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.
The practical version
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.
What I am not sure about
So the question, as narrowly as I can put it: what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss. Practical detail welcome, however dull — the duller the better.
Dr.RaviCardio said:Steady state is the thing most people miss.
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.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
Dr.RaviCardio said:Steady state is the thing most people miss.
Pushing back on Dr.RaviCardio here. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.
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Shop Reference StandardsAnswering the narrow version, because the broad one does not have a single answer. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.
LipidDoc_ATL said:All true, with one condition: that curve is for people who reached the dose on schedule.
That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.
Ask again with the specifics and you will get a better answer than this one.