Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
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 would rather have one careful answer than five confident ones.
PeptideChemSF said:The manufacturing argument is the underrated one.
Correct as far as it goes. The part it does not cover is what to do when the honest answer is "not enough data", which is more often than anyone likes.
PeptideChemSF said:The manufacturing argument is the underrated one.
Pushing back on PeptideChemSF 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.
Happy to go further on any of that.
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Browse GL BiochemThis one has a reasonably settled answer, so here it is. 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.
FDA_TrackerJim said:The part it does not cover is what to do when the honest answer is "not enough data", which is more often than anyone likes.
Adding a me-too, because a thread of one person's experience is not much use. I had assumed I was the exception until I read this.