Nothing to add, except that this is the answer I would give if asked.
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Compounds · Tirzepatide · continued
Tirzepatide in type 2 diabetes: the SURPASS programme, summarised honestly posts 61–90
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 arithmetic in post #59 is right; the assumption feeding it is the part to check.
The five maintenance doses in the tirzepatide programme give a genuine dose-response curve, which is unusual. Most trials in this space compare one or two doses against placebo and cannot say anything about the shape of the relationship.
I would hold that lightly until someone with a larger sample weighs in.
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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.
This is the sort of thing that ought to be settled and apparently is not.
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k.vanhecke, post #15: Post #13 is the version of this I will quote in future. One addition. 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 that is already documented somewhere, ignore me and… Go to post
On tirzepatide in type 2 diabetes the community has more anecdote than the confidence in this thread implies, and I include my own contribution in that.
Post #63 describes the usual case. This is about the unusual one.
An honest declaration on tirzepatide in type 2 diabetes: I have a prior here and it is strong enough that you should weight what I say downward. Stating it rather than hiding it.
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Gastrointestinal effects were comparable in character to the GLP-1 monoagonists across the programme. Individual reports here vary in both directions, which is what you would expect from a between-person difference rather than a between-drug one.
I would not lead a decision with this, but I would not ignore it either.
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Heart rate rises modestly across this class, tirzepatide included. It is consistent, small, and worth knowing about rather than worth alarm — and it is one of the reasons the trials monitored it explicitly.
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ar.kravchenko, post #23: Heart rate rises modestly across this class, tirzepatide included. It is consistent, small, and worth knowing about rather than worth alarm — and it is one of the reasons the trials monitored it explicitly. That is the version I use. It may not be the version that is correct. Go to post
Confirming post #67 from a second method, which matters more than confirming it from a second person.
The titration schedule has more steps than semaglutide's, which reflects the finer gradation used in the clinical programme rather than a pharmacological requirement for smaller steps.
Tirzepatide in type 2 diabetes: I have looked for the primary source twice and failed twice. Either it does not exist or it is somewhere I do not know to look, and I would like to know which.
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tracked_parcel, post #67: Heart rate rises modestly across this class, tirzepatide included. It is consistent, small, and worth knowing about rather than worth alarm — and it is one of the reasons the trials monitored it explicitly. Go to post
Where I part company with post #68, and it is a narrow parting.
The GIP component: GIP receptor agonism is thought to amplify the GLP-1 effect on satiety and energy expenditure, but how much of tirzepatide's effect is that and how much is simply achieving higher receptor occupancy remains genuinely open. The mechanistic literature is active.
Where I have landed on tirzepatide in type 2 diabetes, having got it wrong once in public: the direction is clear, the magnitude is not, and anyone quoting a precise magnitude has borrowed it from somewhere that did not measure it.
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Worth separating tirzepatide in type 2 diabetes as a question about the compound from tirzepatide in type 2 diabetes as a question about the documentation. They get answered by different people and only one of them is answerable here.
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k.otieno_stats, post #61: Nothing to add, except that this is the answer I would give if asked. Go to post
Building on post #74 rather than restating it.
Heart rate rises modestly across this class, tirzepatide included. It is consistent, small, and worth knowing about rather than worth alarm — and it is one of the reasons the trials monitored it explicitly.
m.yilmaz, post #4: Marking my place. If it changes for me I will come back and say so. Go to post
Post #72 put the caveat in the right place and I want to underline 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.
I keep a log for tirzepatide in type 2 diabetes specifically because my memory of it turned out to be systematically wrong in one direction. Six weeks of notes cost nothing and settled it.
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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.
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a.pereira, post #44: This follows post #42 rather than contradicting it. 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… Go to post
Appreciated. The plain phrasing does more work here than a longer post would.
citation_index, post #26: Nausea profile: some people report tirzepatide as less nausea-prone than semaglutide, others report it as more. The trial reported gastrointestinal effects broadly comparable in character. Individual variation is the largest factor. I am not the right person to answer the follow-up to this. Go to post
Building on post #81 rather than restating it.
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.
Flagging that the sources on this are thinner than the confidence in the thread suggests.
Collapsed as off-topic by two members at trust level 3 or above
The titration schedule has more steps than semaglutide's, which reflects the finer gradation used in the clinical programme rather than a pharmacological requirement for smaller steps.
c.wijnberg, post #55: Nausea profile: some people report tirzepatide as less nausea-prone than semaglutide, others report it as more. The trial reported gastrointestinal effects broadly comparable in character. Individual variation is the largest factor. That is the practical version. The rigorous version is longer and says the same thing. Go to post
Post #86 and I disagree about the size of the effect, not about the direction.
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.
It is a small point and it changes the answer, which is an awkward combination.
Taking post #86 at face value and following it one step further.
Tirzepatide's half-life of roughly five days means steady state is approached in about three weeks rather than four. That is a real difference from semaglutide and it is small enough that the weekly schedule is unaffected.
The rule of thumb is fine; the edge cases are where it earns its keep.
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m.ekstrom, post #78: Comparisons between the tirzepatide and semaglutide programmes across trials rather than within one are weak. Different populations, different durations, different baseline characteristics; the only fair comparison is a head-to-head one. Go to post
Half-life difference: tirzepatide is about 5 days versus semaglutide's week-long. Practically, that means steady state is reached slightly faster and the post-dose swing is slightly larger. Most people do not report noticing the difference in practical terms.
I am reporting what happened, not recommending it.