Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.
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.
Where I think it is weakest: the comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
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. Numbers rather than impressions, if you have them.
SarahChen_PharmD said:The manufacturing argument is the underrated one.
Agreed, and ALT falling is not the same as fibrosis improving. Enzymes are a crude proxy; FIB-4 or elastography is what tells you about the thing that matters.
SarahChen_PharmD said:The manufacturing argument is the underrated one.
Pushing back on SarahChen_PharmD here. 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 ResultsAnswering the narrow version, because the broad one does not have a single answer. 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.
RetaRick_CA said:Agreed, and ALT falling is not the same as fibrosis improving.
Second this.