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Topic summary

Triple agonism: additive, synergistic, or neither?

This is a generated summary. It shows the 9 most-liked posts from a topic of 81, 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.
AK
a.kowalskiTL2 Moderator Solution10 Dec 2024#3
e.kjeldsen, post #1: The question in the title: Triple agonism: additive, synergistic, or neither? I will give what I have already checked below so nobody repeats it. Session topic: STEP 4 ( JAMA , 2021). Please read it before posting; the discussion is much better when everyone has. The question I would like us to start with is what the trial set out to… Go to post

Worth separating two things that the opening post runs together.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

7 likes in reply to #1 20mo
SA
s.antonsenTL2 Moderator8 Jan 2025#9

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

25 likes 19mo
CL
customs_ledgerTL3Regular29 Jan 2025#14

Worth separating two things that post #10 runs together.

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.

28 likes 18mo
HF
h.falkTL2 Moderator8 Apr 2025#34
w.novak, post #12: 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. Go to post

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.

31 likes in reply to #12 16mo
AB
a.batistaTL2 Moderator23 Apr 2025#39

post #38 answers the question as asked. The question underneath it is different.

What we do not know about retatrutide, listed explicitly: long-term safety, real-world response rates, the dose response in diverse populations, whether the heart-rate signal persists or attenuates, durability of effect on withdrawal, efficacy in comorbidities beyond obesity.

32 likes 15mo
NV
n.vogelTL2 Moderator6 May 2025#43
forest_plot, post #10: What we do not know about retatrutide, listed explicitly: long-term safety, real-world response rates, the dose response in diverse populations, whether the heart-rate signal persists or attenuates, durability of effect on withdrawal, efficacy in comorbidities beyond obesity. Go to post

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.

24 likes in reply to #10 15mo
MG
m.guerreroTL2 Moderator4 Jun 2025#53
e.ferreira, post #33: 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. 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.

26 likes in reply to #33 14mo
PN
priorauth_notesTL2Regular10 Jul 2025#66
c.adebayo, post #47: I read post #45 twice before replying, because I had assumed the opposite. 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. Go to post

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.

31 likes in reply to #47 13mo
AJ
a.jansenTL2 Moderator11 Aug 2025#78
crossover_review, post #58: 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. Go to post

Practical note that does not fit anywhere else. Whatever you conclude from this topic, write down what you did and when. The single most useful thing in your own records is not any individual result; it is that they are dated and consecutive.

25 likes in reply to #58 12mo

Read the full topic (81 posts)

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