Building on post #5 rather than restating it. 2.5 mg starting dose is well covered in the tag pages, and the older discussions are better than the recent ones because they were argued out properly. Worth twenty minutes before adding to this one.
The 2.5 mg starting dose is not a therapeutic dose — why that matters Writing it up because I had to work it out twice and would rather nobody else did.
A follow-up question about 2.5 mg starting dose that I did not know to ask the first time.
The earlier thread answered what I asked. What I should have asked is below, and I think it is the one that matters.
Where I part company with the opening post, and it is a narrow parting.
My experience of 2.5 mg starting dose contradicts the reply above. I am posting it as a data point rather than as a refutation, because one person's experience is exactly that.
The opening post is the version of this I will quote in future. One addition.
The 2.5 mg starting dose is a tolerance step and not a therapeutic one. Judging efficacy at that dose is the single commonest reasoning error in this subcategory.
A weak preference rather than a position.
Answering the question the opening post raises rather than the one it answers.
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.
This is the version I would want a new member to read first.
What I would want before treating 2.5 mg starting dose as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.
Building on post #5 rather than restating it.
2.5 mg starting dose is well covered in the tag pages, and the older discussions are better than the recent ones because they were argued out properly. Worth twenty minutes before adding to this one.
Worth separating two things that post #5 runs together.
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.
Someone should write this up properly, and it should probably not be me.
This follows post #9 rather than contradicting it.
The published pharmacokinetics show dose proportionality across the studied range, which means dose arithmetic behaves the way you would naively expect. That is not true of every compound and it is worth knowing which ones it is true of.
I am reporting what happened, not recommending it.
Taking post #10 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.
If it helps: the failure mode here is usually boring rather than dramatic.
One caution on 2.5 mg starting dose: everything above assumes the underlying documentation is what it claims to be. That assumption is doing real work and is rarely stated.
SURPASS-2's comparator choice is the criticism that survives. Semaglutide 1.0 mg was the licensed diabetes dose at the time and it was not the highest dose available in the class, so the trial answers a narrower question than the headline implies.
I read post #12 twice before replying, because I had assumed the opposite.
The 2.5 mg starting dose is not a therapeutic dose in the sense that weight loss is minimal at that dose. It is a tolerance-testing dose. Confusing the purpose of a starting dose with the purpose of a maintenance dose leads to false conclusions about efficacy.
Adding a small correction to the 2.5 mg starting dose summary above rather than a disagreement with it. The substance holds; one of the figures is out by a factor that matters.
Thank you — that answers what I came here to find out.
Narrowing post #14, because the general version has more than one answer.
SURPASS-2 compared tirzepatide with semaglutide 1.0 mg, the licensed diabetes dose at that time. It did not compare with semaglutide 2.4 mg, the highest approved dose. That is the central and legitimate criticism of the head-to-head evidence and it is worth remembering when people quote the trial.
Everything in post #17 holds. The case it does not cover is the one I have.
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.
On reflection I would soften that slightly.
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.
Reporting rather than recommending, on 2.5 mg starting dose. What happened is above. Whether it should have is a different question and not one I am qualified to answer.
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.
I checked the source rather than the summary, and they differ.
The honest answer on 2.5 mg starting dose is that it depends, and the useful part is the list of what it depends on. Four items, in rough order of how much they matter.
Most people get the first two right and then argue about the fourth.
Post #21 answers the question as asked. The question underneath it is different.
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 reasoning is more useful than the number, which is why I have shown it.
Worth separating two things that post #21 runs together.
Titration schedules for tirzepatide have more dose steps than semaglutide partly because the compound is more potent and partly because the clinical programme used a finer gradation. That does not mean you cannot escalate on a coarser schedule if that suits you — the published schedule is not a lower bound.
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.
A note on how 2.5 mg starting dose gets discussed rather than on 2.5 mg starting dose itself: the confident posts get the replies and the careful ones get ignored, and the careful ones have been right more often.
On post #25 — agreed on the reasoning, with one qualification.
Dual agonism versus dose: how much of tirzepatide's effect is the GIP component and how much is simply achieving higher receptor engagement? The honest answer is that the question is not settled. Some of the effect is surely the GIP component, but the trial design does not decompose it.
Nothing above should be read as advice about what anyone else should do.
Picking up post #29: that is the part I would want checked first.
2.5 mg starting dose is a question about a distribution, not about a value, and treating it as a value is what produces the confident wrong answers.