Answering the narrow version, because the broad one does not have a single answer. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.

LipidDoc_ATL said:

Read four things before the headline number.

LipidDoc_ATL has the substance of this right. The condition it depends on is worth stating. The phase 2 numbers were about 24% mean weight loss at 48 weeks on the top dose, with the curve still descending at the end of the study. A curve that has not flattened is a real finding, but it also means the true plateau is unknown, and phase 2 populations are small and selected.

rick_sfbay said:

Sceptical rather than excited about the triple agonist, and I would like somebody to talk me out of the scepticism with data rather than enthusiasm.

Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.

Happy to go further on any of that.

From the other side of the consultation, briefly. The mechanism and the magnitude are separate questions. Agreeing that something happens says nothing about whether it happens enough to act on.