This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1.
I read post #27 twice before replying, because I had assumed the opposite.
SURMOUNT-4's randomised withdrawal design is the strongest available evidence about what happens on stopping. It says nothing about a lower maintenance dose, because the comparison was continue versus placebo rather than continue versus less.
The short answer was in the first line; everything after is the working.
I will take the caveat as seriously as the claim, which is the point of putting it there.
An update on my earlier reading SURMOUNT-1 without the press post: the pattern held for another six weeks and then stopped, which I did not predict and cannot explain.
Research-use-only tirzepatide is not approved for human use and is not made to pharmaceutical standards. Anyone discussing it here is describing what they did, not recommending it.
I am describing what is, rather than arguing for what should be.
I think the reading SURMOUNT-1 without the press question is answerable and has not been answered, which is a more optimistic position than most of this thread.
Taking post #35 at face value and following it one step further.
Weight reduction figures from SURMOUNT-1 are frequently quoted without the trial's duration attached. A mean change at 72 weeks and a mean change at 40 weeks are different numbers and both circulate.
I would rather this thread reach "we do not know" about reading SURMOUNT-1 without the press than reach a confident answer that nobody can support when asked.
Confirming post #39 from a second method, which matters more than confirming it from a second person.
The most useful thing anyone has posted about reading SURMOUNT-1 without the press in this category was a table of what had been measured and by whom. That is what I would want again.
Building on post #40 rather than restating it.
Categorical response thresholds — the proportion reaching ten, fifteen or twenty per cent reduction — are more persuasive and less informative than the mean. They depend entirely on where the threshold was drawn.
Everything in post #42 holds. The case it does not cover is the one I have.
Storage and stability: published data on licensed tirzepatide formulations exists and is worth reading directly rather than through summarised claims. Reconstituted preparations in different diluents have not been studied and extrapolation from the licensed formulation is the best you can do.
Small point, but it is the one that usually catches people.
I would call the community position on reading SURMOUNT-1 without the press likely rather than established, and I would be comfortable defending that hedge.
The arithmetic in post #44 is right; the assumption feeding it is the part to check.
Categorical response thresholds — the proportion reaching ten, fifteen or twenty per cent reduction — are more persuasive and less informative than the mean. They depend entirely on where the threshold was drawn.
Written from notes rather than memory, which is why the numbers are specific.
Answering the question post #46 raises rather than the one it answers.
The version of reading SURMOUNT-1 without the press that circulates here is a simplification of a simplification. It is not wrong, but it has lost the conditions under which it holds, and those conditions are where the interesting cases live.
SURMOUNT-1 reported weight reduction of a magnitude that was the largest for a pharmacological intervention at that time of publication. It also reported a clear dose response across three doses. The categorical thresholds (people reaching 10%, 15%, 20% loss) got the most attention but read less informatively than the mean weight change.
It is worth checking rather than assuming, which costs nothing.
The most useful reply I ever got about reading SURMOUNT-1 without the press was a request to state my units. It sounds like pedantry and it has saved me twice.
SURMOUNT-4 used a randomised withdrawal design: everyone titrated, then those on maintenance were randomised to continue or placebo. Continuation maintained effect; withdrawal was followed by regain. The finding is robust but it says nothing about a lower effective maintenance dose, because that was not studied.
Two people can read the same figure differently here and both be reasonable.
Post #49 describes the usual case. This is about the unusual one.
Research-use-only tirzepatide is not approved for human use and is not made to pharmaceutical standards. Anyone discussing it here is describing what they did, not recommending it.
I would treat that as a working assumption and revisit it.
Adding the measurement that post #51 says would settle it.
On reading SURMOUNT-1 without the press, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit.
If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion.
Where the reading SURMOUNT-1 without the press reasoning breaks down for me is the step from the group result to the individual case. That step is almost never argued for.
Answering the question post #54 raises rather than the one it answers.
A note on scope: what I am saying about reading SURMOUNT-1 without the press applies to the case in the first post and I would not extend it further without checking.
SURMOUNT-OSA is notable because it used an objective physiological endpoint, the apnoea-hypopnoea index, rather than a symptom scale. Two parallel trials, with and without positive airway pressure, addressed the confounder directly. The reduction was substantial in both.
Noting that the question and the thing people usually mean by it are different.
Taking post #57 at face value and following it one step further.
Categorical response thresholds — the proportion reaching ten, fifteen or twenty per cent reduction — are more persuasive and less informative than the mean. They depend entirely on where the threshold was drawn.
The part I am sure of is shorter than the part I have written.