What the GIP component of tirzepatide is thought to contribute, and how confident we can be I have a specific reason for asking rather than idle curiosity, and the context is below.
I would like to know what people here actually do about GIP component of tirzepatide, as distinct from what is usually recommended. Those have diverged in every other subject I have looked at closely.
Mine is below, with the reasoning, including the parts I am not confident about.
Reading rather than contributing, but this is the most useful thread I have found on it.
Post #5 and I disagree about the size of the effect, not about the direction.
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.
Not the answer, but possibly the question that gets there.
The dual agonism is not a marketing framing — GIP receptor and GLP-1 receptor engagement are both demonstrable. What is genuinely unresolved is how much of the clinical effect the GIP limb contributes, because no trial decomposes it.
I looked this up rather than remembered it, which is the right order.
Post #16 and I disagree about the size of the effect, not about the direction.
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.
Take the reasoning and check the arithmetic; I do not always get it right.
Read the full topic (21 posts)
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SURMOUNT-4 and what withdrawal data does and does not tell an individual
SURMOUNT-4 and what withdrawal data does and does not tell an individual — setting out what I have, and where I think it stops being reliable. I would like to disagree carefully with the settled view on…
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4 | 42k | 11mo | |
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Tirzepatide in type 2 diabetes: the SURPASS programme, summarised honestly — the long version
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+85 | 90 | 13k | 7mo |
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Tirzepatide in obstructive sleep apnoea: reading SURMOUNT-OSA
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+4 | 8 | 14k | 8mo |
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The 2.5 mg starting dose is not a therapeutic dose — why that matters
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+119 | 136 | 5.6k | 2mo |
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Revisiting: Why tirzepatide titration schedules have more steps than semaglutide's
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+89 | 101 | 32k | 8mo |
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Peak-to-trough ratio at steady state for a weekly agent
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+58 | 64 | 9.7k | 2mo |
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Why fasting instructions for oral semaglutide are not optional advice — does this still hold?
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+98 | 106 | 3.1k | 10mo |
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Second pass at: Trial registration and comparing the protocol with the paper
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+30 | 34 | 33k | 13mo |
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Coming back to: Semaglutide in people without diabetes: what the evidence base looks like
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+41 | 46 | 1.2k | 4mo |
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Journal club: STEP 1 and the treatment-policy estimand — does this still hold?
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+118 | 132 | 12k | 15mo |