Is "synergy" the right word for the combination data?

Is "synergy" the right word for the combination data? — that is the question, and I have not found it answered plainly anywhere I have looked.

Session topic: SCALE (N Engl J Med, 2015). 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 estimate, rather than what it found. Once that is on the table we can talk about whether the design could have answered it, and only then about the numbers.

Specific things I would like covered: the population and how far it generalises, how discontinuation was handled, whether the comparator was a fair one, and what the absolute rather than relative effect looks like.

I will summarise at the end and the summary will feed the relevant digest page.

I read post #3 twice before replying, because I had assumed the opposite.

Reading the phase 2 paper: it establishes tolerability and efficacy in a selected population on a defined dose escalation. It does not establish the lowest effective dose or the durability over years.

Gastric emptying: both amylin and GLP-1 slow it, through partly overlapping but distinct mechanisms. Whether the slowing at a higher magnitude produces disproportionate nausea or is tolerable is a question phase 3 exists to answer.

Coming back to post #6, because the follow-up matters more than the original answer.

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.

Worth separating two things that post #6 runs together.

Is synergy the right word for the combination data? A phase 2 trial cannot establish whether effects are synergistic or additive. Synergy is a mechanistic claim that requires a designed experiment to support it. The combination works, but the mechanism is unsettled.