Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
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.
Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
What I am trying to establish is whether a non-peptide oral agonist can match injectable exposure in practice, or whether the convenience is bought with a lower ceiling. I have searched first, so if this is covered somewhere point me at it and I will read it.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
PeptideChemSF said: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…
True, with the qualification that this is a self-selected group. The people for whom it did not work post less, and that shapes everything we think we know.
PeptideChemSF said: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…
This is where I part company with the consensus forming above. Small molecule does not automatically mean cheap. Price is set by what the market will bear and by patent life, not by cost of goods, and I would not assume the savings reach patients.
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View ResultsThis one has a reasonably settled answer, so here it is. The manufacturing argument is the underrated one. Peptide synthesis capacity has been the binding constraint on this entire class, and a small molecule is made in ordinary chemical plants. If it holds up in phase 3, the supply and price picture changes more than the efficacy picture does.
Dr.CardioMD said:True, with the qualification that this is a self-selected group.
Can confirm. Same sequence, different timescale. Posting only so the count is not one.