Journal club: orforglipron phase 2 and the non-peptide question posts 31–60

Picking up post #29: that is the part I would want checked first.

The figures usually contain the finding and the text usually contains the interpretation. Separating them for the first twenty minutes is a discipline worth keeping.

Marking my uncertainty on orforglipron phase 2 explicitly. I am confident about the direction, much less confident about the size, and not confident at all that it generalises past the case in the first post.

TRIUMPH (ongoing): Retatrutide phase 3. No results yet. Nothing should be attributed to it because it has not finished. When it does, this discussion will return to it.

That is all I can say without guessing.

The reason orforglipron phase 2 keeps being re-asked is that the answer is conditional and people quote it without the condition. It is not that the answer is unknown.

What I would want before treating orforglipron phase 2 as settled: the method, the sample, and whether anyone tried to find the opposite result. Two of the three are usually missing.

Reading back through, this was answered upthread and I missed it. My fault.

The baseline characteristics table is the single most useful page for the questions that get asked here, because it tells you who the result applies to.

Worth checking against a second source before it gets quoted onward.

I had written a reply contradicting post #34 and deleted it. Here is what survived.

My experience of orforglipron phase 2 contradicts the reply above. I am posting it as a data point rather than as a refutation, because one person's experience is exactly that.

The most common failure mode is spending fifty minutes on the effect size and ten on the population. Reversing that ratio would improve most sessions.

If that is already documented somewhere, ignore me and link it.

Bringing the previous paper on the same question makes the session much better and doubles the preparation. Worth doing every third session rather than every one.

Somebody will have a better source than mine, and I hope they post it.

Post #39 put the caveat in the right place and I want to underline it.

The honest answer on orforglipron phase 2 is that it depends, and the useful part is the list of what it depends on. Four items, in rough order of how much they matter.

Most people get the first two right and then argue about the fourth.

Building on post #39 rather than restating it.

Checked the orforglipron phase 2 claim against the primary source this morning. It survives, with a narrower scope than the version quoted here. Posting the narrower scope.

Critical appraisal template: (1) What did the trial set out to estimate? (2) Could the design answer that question? (3) Was the population sufficiently similar to your population to apply the results? (4) What was the absolute effect, not just the relative one? (5) What are the two strongest criticisms available?

It reads as pedantry until the day it does not.

On orforglipron phase 2 I would separate what is worth knowing from what is worth acting on. The first list is long and the second is short, and conflating them is how threads get heated.