How to read a phase 2 result without treating it as a phase 3 result — what changed since posts 31–36

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.

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.

Coming back to post #30, because the follow-up matters more than the original answer.

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.

It is the kind of thing that is obvious once and never again.

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.

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.

That is all I can say without guessing.

This follows post #33 rather than contradicting it.

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 would rather say I do not know than round it up to an answer.