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.
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Compounds · Tirzepatide · continued
Tirzepatide in type 2 diabetes: the SURPASS programme, summarised honestly posts 121–150
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.
On post #118 — agreed on the reasoning, with one qualification.
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 claim is narrower than it sounds, and deliberately so.
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i.lehtinen, post #31: Post #30 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. Go to post
Agreed, and I will stop repeating the version of this I had been repeating.
outline_first, post #59: Confirming post #56 from a second method, which matters more than confirming it from a second person. 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. Reading it… Go to post
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 want a second opinion before relying on that.
Storage and stability: published data on licensed tirzepatide formulations exists and is worth reading directly rather than through summarised claims. Reconstituted preparations in different diluents have not been studied and extrapolation from the licensed formulation is the best you can do.
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Mass and charge states: tirzepatide is about 4813.5 Da and on an electrospray instrument you would expect to see charge states mostly in the 2+ to 4+ range, the same as semaglutide. A doubly charged species would appear at about (4813.5 + 2 × 1.008) / 2 ≈ 2408.
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o.nyberg, post #19: The number people quote for tirzepatide in type 2 diabetes is a central estimate presented without its interval, and the interval is wide enough that the estimate is nearly uninformative on its own. Go to post
Post #124 is right about the mechanism and I think understates the practical bit.
Answering the tirzepatide in type 2 diabetes question as asked, then the question I think is meant. As asked: yes, with the qualification below. As meant: it depends on how the first measurement was taken.
Coming back to post #126, because the follow-up matters more than the original answer.
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.
This is where my knowledge stops and I would rather mark the edge than blur it.
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Following, with nothing to contribute beyond having asked the same thing elsewhere.
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Collapsed as off-topic by two members at trust level 3 or above
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.
q.zhao_qa, post #45: Tirzepatide in type 2 diabetes is one of those subjects where the general answer and the answer for a specific case diverge, and the thread will go in circles until someone says which one is being asked for. Go to post
Careful with the language on tirzepatide in type 2 diabetes. "Not detected" and "not present" are different findings and the first is a statement about the method.
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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k.otieno_stats, post #61: Nothing to add, except that this is the answer I would give if asked. 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 would put a moderate confidence on that and no more.
Post #137 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 checked the source rather than the summary, and they differ.
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r.frisk, post #14: On post #10 — agreed on the reasoning, with one qualification. Tirzepatide in type 2 diabetes is a good example of a question where the honest answer is boring and the interesting answers are unsupported. I would go with boring. 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.
That is the honest state of it as of this week.
Ibrahimovi, post #122: On post #118 — agreed on the reasoning, with one qualification. 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 claim is narrower than it sounds, and deliberately so. Go to post
I would keep tirzepatide in type 2 diabetes 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.
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 deliberately not rounded that, because the rounding is where the argument starts.
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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
Whatever the answer on tirzepatide in type 2 diabetes turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, invite the correction.
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.
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Post #142 is the version of this I will quote in future. One addition.
Small methodological point on tirzepatide in type 2 diabetes: repeating a measurement is cheap and resolves most of what is being argued about here at no cost to anyone.
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il.dumitru, post #10: On tirzepatide in type 2 diabetes, 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… Go to post
Where I part company with post #144, and it is a narrow parting.
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.
I would want to see it done twice before believing it once.
This is the answer, and the reason it is the answer is the more useful part.
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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 would treat the number as indicative rather than as a measurement.
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m.oyelaran, post #25: 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. The mechanism is plausible, which is… Go to post
Right — I had this wrong and I am glad to have read it before it mattered.