Topic summary

Second pass at: Triple agonism: additive, synergistic, or neither?

Compounds › Retatrutide TRIUMPH programme effect size retatrutide randomised trial preprint Solved Under review

This is a generated summary. It shows the 9 most-liked posts from a topic of 121, in their original order, with the accepted answer included where one exists. It is a reading aid and it will miss nuance — the full topic is the record.

s.bruunTL2 Solution9 Jan 2025#4

b.demir, post #3: Picking up the opening post: that is the part I would want checked first. Retatrutide is investigational. Anything obtained outside a trial is by definition research-use-only material with no human-use authorisation. This site will state that plainly rather than winking at it. Anyone who has looked at this more carefully, please correct… Go to post

Triple agonism is a question about a distribution, not about a value, and treating it as a value is what produces the confident wrong answers.

11 likes in reply to #3 19mo

b.correiaTL218 Feb 2025#16

I came in to disagree and I am leaving without a disagreement.

30 likes 17mo

w.moreauTL212 Mar 2025#24

Taking Triple agonism seriously for a moment rather than deflecting: the honest position is that the community has observations and no controlled comparison, and those two things support very different sentences.

30 likes 17mo

blank_injectionTL2Analytical chemist11 Apr 2025#36

The hepatic-steatosis rationale follows directly from glucagon receptor agonism promoting fat oxidation in the liver. Mechanistic plausibility in this field has a poor record of predicting clinical outcomes, which is why the trials matter more than the mechanism.

One of those cases where knowing the mechanism does not help the decision.

28 likes 16mo

da.bakkerTL227 May 2025#56

Post #53 is the version of this I will quote in future. One addition.

Second-hand on Triple agonism, so weight it accordingly — someone whose method I trust told me this and I have not verified it myself.

31 likes 14mo

h.bakkerTL213 Jun 2025#64

Nothing to add on the substance. Thank you for taking the question at face value.

28 likes 13mo

a.kowalczykTL2Regular23 Jun 2025#69

The honest answer on Triple agonism is that it depends, and the useful part is the list of what it depends on. Four items, in rough order of how much they matter.

Most people get the first two right and then argue about the fourth.

29 likes 13mo

f.lindholmTL26 Jul 2025 · edited#75

A request rather than an answer: could whoever has the primary source for Triple agonism post it? I have seen the claim three times this month and each version had lost a qualifier.

27 likes 13mo

ew.kuuselaTL220 Sep 2025#114

m.perrin, post #88: Where I part company with post #86, and it is a narrow parting. 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. Go to post

Nausea and vomiting were dose-related in the phase 2 work, as they are throughout this class. What is not established is whether the tolerability profile differs from the dual agonists at equipotent effect, because equipotence has not been established either.

I looked this up rather than remembered it, which is the right order.

28 likes in reply to #88 10mo

Read the full topic (121 posts)

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