The opening post and I disagree about the size of the effect, not about the direction.
Triple agonism: is the effect additive, synergistic, or neither? A phase 2 comparison of tirzepatide (dual) to retatrutide (triple) would answer that question. The published data does not include such a direct comparison.
Hepatic effects: glucagon receptor agonism promotes hepatic fat oxidation, which is mechanistically plausible for benefit in metabolic liver disease. Whether that translates to improved clinical outcomes is being tested in phase 2 work.
I would treat that as a working assumption and revisit it.
Why this subcategory is more cautious than elsewhere: retatrutide is investigational, phase 3 is ongoing, and the heart-rate signal in phase 2 is not negligible. Caution is proportionate to the evidence status.
The phase 2 obesity data is genuinely striking and it is phase 2 data. Sample sizes at that stage characterise a dose-response relationship; they do not characterise a safety profile, and treating them as though they did is the error to avoid here.
The phase 3 programme is ongoing and its results will change what can be said here. Until then, this subcategory's convention is to state the phase alongside any result quoted.
I would want a second opinion before relying on that.
Read the full topic (36 posts)
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Why retatrutide discussion here is more cautious than elsewhere — one year on
Asking directly, because I could not find a straight answer: Why retatrutide discussion here is more cautious than elsewhere — one year on Two things I would like separated before anyone answers on…
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+92 | 97 | 3.6k | 20h |
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The retatrutide phase 2 obesity paper, read closely
Posting this under the heading it deserves: The retatrutide phase 2 obesity paper, read closely Everything below is what sits behind that. Retatrutide phase 2 obesity paper, from the point of view of someone…
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2 | 65k | 10mo | |
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Why a glucagon receptor agonist in a weight-loss compound is not a contradiction — one year on
The question in the title: Why a glucagon receptor agonist in a weight-loss compound is not a contradiction — one year on I will give what I have already checked below so nobody repeats it. Glucagon receptor…
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4 | 3.7k | 10mo | |
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Follow-up: The retatrutide phase 2 obesity paper, read closely
The retatrutide phase 2 obesity paper, read closely — setting out what I have, and where I think it stops being reliable. A follow-up question about retatrutide phase 2 obesity paper that I did not know to…
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+19 | 23 | 16k | 2d |
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What TRIUMPH is designed to answer, and why we should not pre-empt it — does this still hold?
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+43 | 47 | 5.5k | just now |
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Oral versus injectable exposure: comparing apples to a different fruit
Oral versus injectable exposure: comparing apples to a different fruit — setting out what I have, and where I think it stops being reliable. Something about oral versus injectable exposure does not reconcile…
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+19 | 23 | 332 | 8mo |
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The 2.5 mg starting dose is not a therapeutic dose — why that matters — a second dataset
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+12 | 16 | 11k | 7mo |
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About the Journal club category
Our recurring session. One named paper per topic, methods first, conclusions last. Everyone reads before posting. This post is a community wiki: any member at trust level 3 or above can edit it, and every…
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+2 | 6 | 12k | 16mo |
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Primary endpoint hierarchies and why order matters
Primary endpoint hierarchies and why order matters Writing it up because I had to work it out twice and would rather nobody else did. I was wrong about primary endpoint hierarchies in a thread last spring and…
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4 | 308 | 3mo | |
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Tirzepatide molecular mass and the charge states you would expect on ESI
Tirzepatide molecular mass and the charge states you would expect on ESI Writing it up because I had to work it out twice and would rather nobody else did. Tirzepatide molecular mass keeps being re-asked here…
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+36 | 40 | 44k | 11mo |