Whatever the answer on 2.5 mg starting dose turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.
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Compounds · Tirzepatide · continued
The 2.5 mg starting dose is not a therapeutic dose — why that matters posts 31–60
This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.
ra.mensa, post #2: On 2.5 mg starting dose: the maintained page in the documentation commons covers the general case with citations and a review date, which is more reliable than any reply here including this one. Go to post
Narrowing post #32, because the general version has more than one answer.
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.
2.5 mg starting dose 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.
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ma.balogun, post #30: 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. Go to post
That matches what I have seen, for whatever a single anecdote is worth.
Post #35 answers the question as asked. The question underneath it is different.
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 keep a log of this specifically because memory is unreliable about it.
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Picking up post #37: that is the part I would want checked first.
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.
Someone will know this better than I do and I hope they say so.
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g.haaland, post #21: 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. Go to post
On post #38 — agreed on the reasoning, with one qualification.
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 want a second opinion before relying on that.
Noted, and I have changed what I was going to do on the strength of it.
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Confirming post #39 from a second method, which matters more than confirming it from a second person.
2.5 mg starting dose looks different depending on whether you are reading the primary literature or the summaries of it, and the difference is not in our favour.
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I would keep 2.5 mg starting dose and the decision it usually gets used for separate in this thread. They are related and they are not the same question, and merging them is why the last one went badly.
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s.vanhecke, post #14: 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. Go to post
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.
On 2.5 mg starting dose the community has more anecdote than the confidence in this thread implies, and I include my own contribution in that.
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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.
That is the shape of it. The detail is where I would expect to be corrected.
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me.eriksen, post #10: 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. Go to post
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.
Posting my 2.5 mg starting dose numbers with the method attached so they can be discounted properly. Uncontrolled, unblinded, and collected by someone who wanted a particular answer.
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Useful. I had the fact and not the reason, which turns out to be the important half.
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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.
I have said this before in a thread nobody could find, so it is worth repeating.
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s.ferreira, post #18: 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. Go to post
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.
Everything in post #52 holds. The case it does not cover is the one I have.
Small correction to my own earlier position on 2.5 mg starting dose. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
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buffer_margin, post #1: 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… Go to post
Taking post #54 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 general answer and the answer for your case may diverge here.
taper_table, post #13: 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. Go to post
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 have no interest in any supplier named above.
Collapsed as off-topic by two members at trust level 3 or above
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.
I read post #56 twice before replying, because I had assumed the opposite.
Adding the boring version of 2.5 mg starting dose, because the interesting version keeps getting posted and the boring one is usually right.
Check the ordinary explanations, in order, and stop when one of them accounts for what you are seeing. Most of the time the second one does.
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I disagree with the framing of 2.5 mg starting dose above, and I think it is a substantive disagreement rather than a terminological one. Setting out why, so it can be checked.
The reasoning depends on an assumption that is doing a lot of work and is never stated. If the assumption holds, the conclusion follows. I do not think it holds generally.
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I had written a reply contradicting post #56 and deleted it. Here is what survived.
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 the number as indicative rather than as a measurement.
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