Compounds · Retatrutide

How to read a phase 2 result without treating it as a phase 3 result — what changed since

Compounds › Retatrutide TRIUMPH programme randomised trial preprint

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Solved by trough_index in post #4

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.

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d.nilsenTL221 Aug 2025#1

Asking directly, because I could not find a straight answer: How to read a phase 2 result without treating it as a phase 3 result — what changed since

Putting the numbers in the first post, because a question about a compound without them turns into a question about somebody's impression of it.

retatrutide, monoisotopic mass near 4731.3 Da, 17 weeks of my own notes, and 4 lots from 3 suppliers with a purity figure on each. That is the whole basis of what follows.

What I want checked is the reasoning I have built on top of it, not the figures themselves.

1 like 11mo

KTurkingtonTL3Regular31 Aug 2025#2

How to read phase 2 without treating it as phase 3: phase 2 establishes that a dose range produces an effect and is tolerable enough to justify large trials. It does not establish safety, durability, or whether real humans differ from the selected population.

Take the reasoning and check the arithmetic; I do not always get it right.

4 likes 11mo

a.norgaardTL28 Sep 2025 · edited#3

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.

The honest answer is that it depends, and here is what it depends on.

12 likes 11mo

trough_indexTL3Regular Solution14 Sep 2025#4

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.

25 likes 10mo

ne.laurentTL220 Sep 2025#5

TRIUMPH is phase 3 and it is ongoing. No phase 3 results exist. Nothing should be attributed to TRIUMPH because the trial has not finished. When it does, this page will update.

Anyone who has looked at this more carefully, please correct the record.

0 likes 10mo

n.bridgewaterTL2Member26 Sep 2025#6

a.norgaard, post #3: 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. The honest answer is that it depends, and here is what it depends on. Go to post

That matches what I have seen, for whatever a single anecdote is worth.

1 like in reply to #3 10mo

s.lundgrenTL22 Oct 2025#7

trough_index, post #4: 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. Go to post

Building on post #5 rather than restating it.

Renal and cardiovascular outcome data does not exist for this compound. Absence of a reported signal in a phase 2 trial of a few hundred people is not evidence of absence.

7 likes in reply to #4 10mo

LJankowiakTL3Regular7 Oct 2025#8

Post #4 put the caveat in the right place and I want to underline it.

No phase 3 results exist for retatrutide. Anything attributed to a completed phase 3 trial of this compound is either a misreading or an invention, and the honest answer to most questions here is that the data is not in yet.

18 likes 10mo

c.bakkerTL212 Oct 2025#9

Phase 2 sample sizes are not adequate for safety characterisation of a novel triple agonist. Phase 3 is where that question gets answered. Using phase 2 results to make claims about safety profile is using the trial for a purpose it was not designed for.

I am not the right person to answer the follow-up to this.

0 likes in reply to #3 10mo

m.brobergTL217 Oct 2025 · edited#10

I had written a reply contradicting post #8 and deleted it. Here is what survived.

Dose-response in the phase 2 obesity work was clear across the studied range, with no obvious plateau within it. Extrapolating beyond the highest studied dose from that is exactly the reasoning trials are designed to prevent.

The mechanism is plausible, which is not the same as established.

0 likes 9mo

m.ekstromTL222 Oct 2025#11

Whether triple agonism is additive or synergistic is an open question and the published work does not answer it. A phase 2 trial without a dual-agonist comparator arm cannot distinguish the two.

I have written this out at length because the short version keeps being misread.

0 likes 9mo

m.eriksenTL227 Oct 2025#12

Anyone deciding on the basis of what is published should know that what is published is a phase 2 programme and some pharmacokinetics. That is a genuinely early evidence base and this page will say so until it changes.

Written quickly, so the reasoning may be tighter than the wording.

20 likes 9mo

a.lindholmTL231 Oct 2025#13

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.

5 likes 9mo

c.delgadoTL25 Nov 2025#14

c.bakker, post #9: Phase 2 sample sizes are not adequate for safety characterisation of a novel triple agonist. Phase 3 is where that question gets answered. Using phase 2 results to make claims about safety profile is using the trial for a purpose it was not designed for. I am not the right person to answer the follow-up to this. Go to post

Understood, and I withdraw the assumption I opened with.

0 likes in reply to #9 9mo

l.dialloTL210 Nov 2025#15

On post #11 — agreed on the reasoning, with one qualification.

Discontinuation for adverse effects in phase 2 was not negligible at the higher doses. That figure belongs next to the efficacy figure whenever the efficacy figure is quoted.

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

0 likes 9mo

c.inglethorpeTL3Regular14 Nov 2025#16

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.

27 likes 8mo

h.amankwahTL218 Nov 2025#17

a.lindholm, post #13: 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. Go to post

The phase 2 obesity paper reported dose-dependent weight reduction of a magnitude that attracted attention. It also reported dose-dependent heart-rate increases. The heart-rate signal is the reason phase 3 exists rather than something assumed negligible based on phase 2.

Noting that the question and the thing people usually mean by it are different.

8 likes in reply to #13 8mo

ThibodeauTL3Regular23 Nov 2025#18

m.broberg, post #10: I had written a reply contradicting post #8 and deleted it. Here is what survived. Dose-response in the phase 2 obesity work was clear across the studied range, with no obvious plateau within it. Extrapolating beyond the highest studied dose from that is exactly the reasoning trials are designed to prevent. The mechanism is plausible,… Go to post

Heart rate increased in a dose-dependent way in the phase 2 work. That is not a footnote — it is one of the specific things phase 3 exists to characterise, and it is why this subcategory is written more cautiously than the others.

2 likes in reply to #10 8mo

owen.bradyTL4 Moderator27 Nov 2025 · edited#19

m.eriksen, post #12: Anyone deciding on the basis of what is published should know that what is published is a phase 2 programme and some pharmacokinetics. That is a genuinely early evidence base and this page will say so until it changes. Written quickly, so the reasoning may be tighter than the wording. Go to post

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.

21 likes in reply to #12 8mo

k.dahlbergTL21 Dec 2025#20

Narrowing post #19, because the general version has more than one answer.

The evidence status here should be stated in the first line of any post about it rather than the last. Everything is phase 2 or earlier, and a reader arriving from a search will not know that unless somebody says so.

9 likes 8mo

glossary_deskTL3Regular6 Dec 2025#21

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.

26 likes 8mo

d.achebeTL210 Dec 2025#22

Collapsed as off-topic by two members at trust level 3 or above

Clear enough that I do not think I have a follow-up, which is unusual.

DKwiatkowskiTL3Regular14 Dec 2025 · edited#23

This is where my knowledge stops and I would rather mark the edge than blur it.

2 likes in reply to #10 7mo

j.lokkenTL218 Dec 2025#24

TRIUMPH is phase 3 and it is ongoing. No phase 3 results exist. Nothing should be attributed to TRIUMPH because the trial has not finished. When it does, this page will update.

I am describing what is, rather than arguing for what should be.

8 likes 7mo

aliquot_lineTL3Regular22 Dec 2025#25

Post #24 is right about the mechanism and I think understates the practical bit.

4 likes 7mo

v.stanescuTL226 Dec 2025#26

LJankowiak, post #8: Post #4 put the caveat in the right place and I want to underline it. No phase 3 results exist for retatrutide. Anything attributed to a completed phase 3 trial of this compound is either a misreading or an invention, and the honest answer to most questions here is that the data is not in yet. Go to post

Coming back to post #23, because the follow-up matters more than the original answer.

Someone will know this better than I do and I hope they say so.

13 likes in reply to #8 7mo

NicolaidesTL3Regular30 Dec 2025#27

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.

27 likes 7mo

f.piresTL23 Jan 2026#28

0 likes 7mo

m.haddadTL2Regular7 Jan 2026#29

Sensible. I would want the same detail before I acted on it either.

0 likes 7mo

k.marchandTL210 Jan 2026#30

I would want the raw data before agreeing with my own summary of it.

1 like in reply to #12 7mo

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