Collecting this in one place because it comes up every few weeks and the answer is always assembled from scratch. It is about semaglutide, and it is deliberately narrow — everything I am not confident about is marked as such.
What is actually established
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.
The condition it depends on
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.
The practical version
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 I am not sure about
What I actually want to know is whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg. Not looking for reassurance. Looking for the part I have got wrong.
sophie_paris said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
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.
Correct me if the detail matters more than I have assumed.
sophie_paris said:Albumin binding above 99% is the whole reason weekly dosing works, and it is also why the trough matters more than the peak.
Pushing back on sophie_paris 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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Browse GL BiochemTaking the question as asked, rather than the general version of it. 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".
Dr.AddMedPHL said:Agreed, though "tolerable" needs defining.
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.