Posting this under the heading it deserves: Reading SURMOUNT-1 without the press release Everything below is what sits behind that.
What changes if the standard account of reading SURMOUNT-1 without the press is wrong? I ask because I have been treating it as settled and I noticed this week that I could not say why.
Working through the consequences rather than the evidence, since others here are better placed on the evidence.
Practical answer on reading SURMOUNT-1 without the press, since the theoretical one is upthread: do the simplest check first, write down the result, and only then decide whether the complicated explanation is needed. It usually is not.
Helpful, and short, which on this subject is harder than long.
The arithmetic in post #3 is right; the assumption feeding it is the part to check.
The failure mode on reading SURMOUNT-1 without the press is boring rather than dramatic. It is almost always the step everyone assumes was done correctly because it is too simple to get wrong.
Answering the question post #2 raises rather than the one it answers.
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.
Not the whole picture, but the part of it I can speak to.
Adding a reference point for reading SURMOUNT-1 without the press. Mine is a single case, collected without controls, and I am posting the method alongside it so it can be discounted appropriately.
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.
One case, stated as one case.
Coming back to post #6, because the follow-up matters more than the original answer.
What I can speak to on reading SURMOUNT-1 without the press is narrow, so I will keep it narrow rather than generalising from it. Beyond that boundary I do not know.
Reading SURMOUNT-1 without the press is a question about a distribution, not about a value, and treating it as a value is what produces the confident wrong answers.
Post #9 and I disagree about the size of the effect, not about the direction.
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.
Written in the hope of being told what I have missed.
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.
The variance between people here is larger than the effect being discussed.
Since reading SURMOUNT-1 without the press keeps coming up, it should probably be a maintained page rather than a recurring thread. I am happy to draft it if someone with more direct experience will review it.
Summarising the reading SURMOUNT-1 without the press thread so far, since it is long and the answer is buried: the first reply has the method, the fourth has the correction to it, and the rest is people agreeing at length.
Nothing to add, except that this is the answer I would give if asked.
Building on post #16 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.
A weak preference rather than a position.
Answering the question post #18 raises rather than the one it answers.
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.
The arithmetic in post #18 is right; the assumption feeding it is the part to check.
The apnoea-hypopnoea index used in SURMOUNT-OSA is an objective measurement rather than a symptom scale, which is why that trial carries more weight than its size suggests. Two parallel trials with and without positive airway pressure addressed the obvious confounder directly.
Stating my assumptions rather than smuggling them in.
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.
I have said this before in a thread nobody could find, so it is worth repeating.
I had written a reply contradicting post #20 and deleted it. Here is what survived.
A definition problem is doing most of the work in this reading SURMOUNT-1 without the press discussion. Once the term is pinned down I suspect the disagreement mostly goes away and what is left is small.
Picking up post #22: that is the part I would want checked first.
What I would check first on reading SURMOUNT-1 without the press is whether the thing being measured moved or whether the way of measuring it moved. Those look identical in a graph.
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.
The uncertainty is in the assumption, not in the calculation.
Reading SURMOUNT-1 without the press was covered in the wiki last year and the page has a review date on it, which is a better starting point than my memory of a thread.
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.
Posted with less confidence than the sentence structure implies.
This follows post #26 rather than contradicting it.
Reading this reading SURMOUNT-1 without the press thread as someone who came in with a fixed view: the third and seventh replies moved me and the confident ones did not.
Following, with nothing to contribute beyond having asked the same thing elsewhere.
Building on post #26 rather than restating it.
Whatever the answer on reading SURMOUNT-1 without the press turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.
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.
This is the sort of thing the wiki should carry and currently does not.