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.
Noted, and thank you for writing it out rather than summarising it.
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 variance between people here is larger than the effect being discussed.
Reading rather than contributing, but this is the most useful thread I have found on it.
Worth separating two things that post #3 runs together.
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.
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.
One case, stated as one case.
On post #6 — agreed on the reasoning, with one qualification.
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.
On post #9 — agreed on the reasoning, with one qualification.
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.
I would treat that as a working assumption and revisit it.
Thank you — that answers what I came here to find out.
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.
Worth separating two things that post #13 runs together.
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.
Post #17 is right about the mechanism and I think understates the practical bit.
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.
Coming back to post #17, because the follow-up matters more than the original answer.
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.
Picking up post #17: that is the part I would want checked first.
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.
Coming back to post #20, because the follow-up matters more than the original answer.
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.
Post #22 answers the question as asked. The question underneath it is different.
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.
Helpful, and easy to find again, which is half of what a good reply is.
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.
A partial answer, offered because a partial answer beats none.
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.
Following this. I have the same question and no better information than the first post.
Worth separating two things that post #25 runs together.
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.
Picking up post #26: that is the part I would want checked first.
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.