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.
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".
"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.
Worth knowing that the injection site changes very little. Abdomen, thigh and upper arm are bioequivalent for semaglutide, so a site change is not a plausible explanation for a bad week.
What would genuinely help is knowing what the dose-response curve actually looks like above 1.7mg, because the trial means hide how few people account for the extra loss. Happy to be told the question itself is wrong.
mike.trainer_LA said:The dose-response is real but shallow at the top.
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.
mike.trainer_LA said:The dose-response is real but shallow at the top.
I read this differently from mike.trainer_LA, on substance rather than tone. 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.
Happy to go further on any of that.
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Browse GL BiochemShort answer first, then the reasoning. 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.
CarlaRPh_TPA 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.