An honest declaration on 2.5 mg starting dose: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
11 likes 3mo
Compounds · Tirzepatide · continued
The 2.5 mg starting dose is not a therapeutic dose — why that matters posts 121–137
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.
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.
The right answer here may simply be that it has not been measured.
7 likes 3mo
s.karlsen_rph, post #65: 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… Go to post
Thank you for taking the time. That was more work than a reply usually is.
Collapsed as off-topic by two members at trust level 3 or above
Post #120 and I disagree about the size of the effect, not about the direction.
2.5 mg starting dose is worth one more sentence than it usually gets, and the sentence is the one about how the number was arrived at.
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.
The answer changed when I changed how I was measuring, which was informative.
0 likes 2mo
The number people quote for 2.5 mg starting dose is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own.
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b.solberg, post #81: 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. Go to post
Building on post #126 rather than restating it.
What I would check first on 2.5 mg starting dose 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 mechanism is plausible, which is not the same as established.
0 likes 2mo
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 would put a moderate confidence on that and no more.
23 likes 2mo
orbitrap_ola, post #67: 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. Go to post
Answering the question post #128 raises rather than the one it answers.
Trying to state the 2.5 mg starting dose position in a way that someone who disagrees would recognise as fair, because I do not think the version in this thread passes that test.
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.
One of those cases where knowing the mechanism does not help the decision.
22 likes 2mo
cannula_notes, post #96: Small methodological point on 2.5 mg starting dose: repeating a measurement is cheap and resolves most of what is being argued about here at no cost to anyone. Go to post
On 2.5 mg starting dose I would separate what is worth knowing from what is worth acting on. The first list is long and the second is short, and conflating them is how threads get heated.
This follows post #131 rather than contradicting 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.
Two people can read the same figure differently here and both be reasonable.
0 likes 2mo
k.salinas, post #9: 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… Go to post
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.
s.grigorescu, post #113: On 2.5 mg starting dose, the part that usually goes wrong is that the question is asked as though it has one answer. It has a range, and the width of the range is the interesting bit. If you can post the two or three numbers you are working from, several people here will check the arithmetic rather than argue about the conclusion. Go to post
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.
Post #135 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.
If anyone has run this properly I would rather read that than my own guess.
3 likes 2mo
This topic was referenced in
- Revisiting: Why tirzepatide titration schedules have more steps than semaglutide'sCompounds › Tirzepatide · 101 replies
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