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.
Coming back to post #58, because the follow-up matters more than the original answer.
Source for the 2.5 mg starting dose figure, since it was asked for. It is in the discussion rather than the abstract, which is why the version circulating is stronger than the paper is.
Reading the surrounding paragraph is worth the two minutes. The authors are more careful than their summarisers.
Post #61 is right about the mechanism and I think understates the practical bit.
A request rather than an answer: could whoever has the primary source for 2.5 mg starting dose post it? I have seen the claim three times this month and each version had lost a qualifier.
No notes. Posting so the count is not one.
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.
I would rather say I do not know than round it up to an answer.
I read post #61 twice before replying, because I had assumed the opposite.
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.
Speaking only to 2.5 mg starting dose as I have actually seen it, rather than as it is usually described: the effect is real, it is smaller than the thread suggests, and the variance between people is larger than the effect.
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 have separated what I observed from what I concluded, which does not always happen.
The confident answers on 2.5 mg starting dose and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.
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.
The short version is the first sentence; the rest is why.
Confirming post #68 from a second method, which matters more than confirming it from a second person.
I would call the community position on 2.5 mg starting dose likely rather than established, and I would be comfortable defending that hedge.
I had written a reply contradicting post #70 and deleted it. Here is what survived.
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.
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 step people skip is the one I have spelled out.
Coming back to post #75, because the follow-up matters more than the original answer.
Since 2.5 mg starting dose 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.
This follows post #76 rather than contradicting it.
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.
Summarising the 2.5 mg starting dose 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.
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 single observation, in a thread that deserves better than single observations.
Practical note on 2.5 mg starting dose: write down what you expect before you look. The number of times I have found what I went looking for is higher than chance would allow.
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 had written a reply contradicting post #79 and deleted it. Here is what survived.
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 general case is well covered; this is the awkward specific one.
Confirming post #83 from a second method, which matters more than confirming it from a second person.
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.
Where I part company with post #83, and it is a narrow parting.
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.
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.
Narrowing post #87, because the general version has more than one 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.
On balance I think that is right, and I would not bet much on it.