Reading the phase 2 write-up next to the injectable trials, and the comparison people keep making does not survive putting the two protocols side by side.
Phase 2: about 14.7% at 36 weeks on 45mg, GI adverse events broadly in line with the injectables, no food-timing requirement.
So the question, as narrowly as I can put it: whether a non-peptide oral agonist can match injectable exposure in practice, or whether the convenience is bought with a lower ceiling.
I would rather have one careful answer than five confident ones.
Short answer first, then the reasoning. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.
PurityPaulOR said:Relative and absolute effects need reading together.
Agreeing with PurityPaulOR, and the qualification matters more than the agreement. Orforglipron is a small molecule rather than a peptide, which is the whole point: no SNAC absorption enhancer, no fasting window, no cold chain, and oral bioavailability in the tens of percent instead of around one. Phase 2 put it near 14.7% weight loss at 36 weeks on the top dose with a side-effect profile that looks like the injectables.
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View ResultstampaLisa73 said:Reading the phase 2 write-up next to the injectable trials, and the comparison people keep making does not survive putting the two protocols side by…
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.
From the other side of the consultation, briefly. The honest answer is that the effect is real, the magnitude is contested, and the individual variation is larger than either. Those three things can all be true at once, and most arguments here are two people holding different parts of that.
That is the short version; the long version is somebody else's post.