On post #2 — agreed on the reasoning, with one qualification.
Mass and identity: a report on retatrutide should state the mass detected by LC-MS, not assume a theoretical mass. The theoretical mass is not published in peer-reviewed literature for retatrutide at present.
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.
Dose escalation in the published trials: the protocols started at lower doses and escalated by defined steps. The step sizes are documented and they may or may not match what someone self-prescribing would choose.
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 disagree with the reply above, and I think the disagreement is substantive rather than terminological.
The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.
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 Session topic: PIONEER 6 ( N Engl J Med , 2019). Please read it…
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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. Session topic: STEP 8 ( JAMA , 2022). Please read it before posting;…
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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. Comparing STEP 4 (…
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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. I have seen STEP 4 ( JAMA , 2021) cited in support of a claim I do not think it…
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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?
Asking directly, because I could not find a straight answer: What TRIUMPH is designed to answer, and why we should not pre-empt it — does this still hold? Session topic: STEP 2 ( Lancet , 2021). Please read…
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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. Comparing SURMOUNT-2 ( Lancet , 2023) with SURMOUNT-4 ( JAMA ,…
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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. Comparing SURMOUNT-OSA ( N Engl J Med , 2024) with SURPASS-2 ( N Engl J…
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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. I have seen SUSTAIN 6 ( N Engl J Med , 2016) cited…
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+36 | 40 | 44k | 11mo |