What TRIUMPH is designed to answer, and why we should not pre-empt it

What TRIUMPH is designed to answer, and why we should not pre-empt it I have a specific reason for asking rather than idle curiosity, and the context is below.

I have seen SURPASS-4 (Lancet, 2021) cited in support of a claim I do not think it supports, twice this month, so I would like to work through what it actually shows.

My reading is that the trial is sound for its own question and is being stretched to answer a different one. I might be wrong about that, which is why this is a topic rather than a correction.

What I would like from this discussion: someone who disagrees with me to say why, with the section of the paper they are relying on.

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.

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

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.

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.

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.

I read post #5 twice before replying, because I had assumed the opposite.

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.

For anyone arriving from a search: the marked solution above is the direct answer, and the replies underneath it add the caveats that make it safe to use.

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.