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.
The question I want answered is whether a non-peptide oral agonist can match injectable exposure in practice, or whether the convenience is bought with a lower ceiling. Not looking for reassurance. Looking for the part I have got wrong.
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.
LipidDoc_ATL said:The manufacturing argument is the underrated one.
Agreed, with the caveat that HbA1c is unreliable in anaemia, haemoglobinopathies and recent blood loss, all of which are commoner than people assume. If it disagrees with fasting glucose or a CGM, that is worth chasing.
LipidDoc_ATL said:The manufacturing argument is the underrated one.
Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. 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.
Janoshik Analytical — Independent Testing
Trusted third-party HPLC & mass spectrometry analysis. Verify peptide purity with the lab the community relies on. Independent. Accurate. Transparent.
Verify Your PeptidesGL Biochem (Shanghai) Ltd. — Direct Manufacturer
Est. 1998. The synthesis house behind the vials you send for testing. ISO 9001 and cGMP certified, 1,500+ staff, batch-specific COA with every order.
Browse GL BiochemShort answer first, then the reasoning. 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.
NeuroNate said:Agreed, with the caveat that HbA1c is unreliable in anaemia, haemoglobinopathies and recent blood loss, all of which are commoner than people assume.
Same pattern here, and in the same order. Nothing to add that would improve it.