The confident answers on tirzepatide in type 2 diabetes and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category.
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Compounds · Tirzepatide · continued
Tirzepatide in type 2 diabetes: the SURPASS programme, summarised honestly posts 91–120
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.
h.ferrari, post #11: Following this. I have the same question and no better information than the first post. Go to post
Small correction to my own earlier position on tirzepatide in type 2 diabetes. I had the units the wrong way round, which changes the conclusion by an order of magnitude and therefore changes it entirely.
Taking post #92 at face value and following it one step further.
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.
One more caveat and then I will stop qualifying: the sample selected itself.
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Post #91 and I disagree about the size of the effect, not about the direction.
Adding the boring version of tirzepatide in type 2 diabetes, 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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Thibodeau, post #75: 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. Go to post
Right, and stated more narrowly than I would have dared to state it.
s.cardoso, post #2: Taking the opening post 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. Go to post
On tirzepatide in type 2 diabetes: 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.
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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Worth separating two things that post #94 runs together.
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.
Adding it because I spent an afternoon working it out and nobody should have to twice.
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Confirming post #96 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.
It cost nothing to check and would have cost something not to.
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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 put the burden of proof on the interesting explanation, not the dull one.
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j.restrepo, post #60: I had written a reply contradicting post #59 and deleted it. Here is what survived. 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
Adding the measurement that post #98 says would settle it.
Adding what did not work for me on tirzepatide in type 2 diabetes, since the failures never get written up and they are half the useful information.
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.
Worth one more sentence than it usually gets.
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Birkeland, post #28: On tirzepatide in type 2 diabetes 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. Go to post
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.
The interesting part of this is the exception, and I do not understand the exception.
h.castellanos, post #52: 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. Worth checking against a second source before it gets quoted onward. Go to post
On purity: the trailing-edge features people report on tirzepatide chromatograms are frequently deamidation products, which elute close to the main peak and are easy to integrate into it. That is a method question rather than a quality question.
It is one reading of the data and not the only reasonable one.
Answering the question post #104 raises rather than the one it answers.
Reframing tirzepatide in type 2 diabetes slightly, because I think the disagreement is about the question rather than the answer. If the question is "does it happen", yes. If it is "how often", nobody here knows.
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The bit of tirzepatide in type 2 diabetes that nobody enjoys is that the answer changes depending on what you are trying to decide with it. Say what the decision is and the thread will converge.
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k.fonseca, post #18: Posting my tirzepatide in type 2 diabetes numbers with the method attached so they can be discounted properly. Uncontrolled, unblinded, and collected by someone who wanted a particular answer. Go to post
Clear enough that I do not think I have a follow-up, which is unusual.
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.
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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.
Happy to be the one who is wrong here if it settles the question.
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Worth separating two things that post #107 runs together.
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.
Not a strong opinion, just a consistent one.
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I changed my mind about tirzepatide in type 2 diabetes after someone here asked me for the source and I could not produce one. That is worth saying out loud because it is the ordinary way it happens.
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g.ibarra, post #3: Everything in the opening post holds. The case it does not cover is the one I have. Source for the tirzepatide in type 2 diabetes 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… Go to post
Speaking only to tirzepatide in type 2 diabetes 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.
d.oyelaran, post #91: The confident answers on tirzepatide in type 2 diabetes and the well-sourced answers are not the same answers, which is the most useful thing I have learned reading this category. Go to post
Post #111 is right about the mechanism and I think understates the practical bit.
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 post #111 — agreed on the reasoning, with one qualification.
Two things can be true about tirzepatide in type 2 diabetes at once: the mechanism is plausible and the evidence for the size of the effect is thin. Most of the argument here is people defending the first against attacks on the second.
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Picking up post #115: that is the part I would want checked first.
A request rather than an answer: could whoever has the primary source for tirzepatide in type 2 diabetes post it? I have seen the claim three times this month and each version had lost a qualifier.
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m.ramos, post #82: Counterpoint on tirzepatide in type 2 diabetes, offered without confidence: the same observation is consistent with a much duller explanation, and nobody has ruled the dull one out. Go to post
On purity: the trailing-edge features people report on tirzepatide chromatograms are frequently deamidation products, which elute close to the main peak and are easy to integrate into it. That is a method question rather than a quality question.
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
The question underneath tirzepatide in type 2 diabetes is usually "how would I tell?" rather than "what is true?", and that one has a method attached to it.
Write down what you would expect to see under each hypothesis before you collect anything. If they predict the same observation, collecting it will not help.
Adding the measurement that post #119 says would settle it.
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.
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