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.
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 comparator does most of the work in how this gets reported, and it is not the comparator most people think they are citing.
The narrow version of the question is whether a non-peptide oral agonist can match injectable exposure in practice, or whether the convenience is bought with a lower ceiling. Practical detail welcome, however dull — the duller the better.
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.
greg_boulder 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…
Agreed, and one caution: a single measurement is not a measurement. Anything that moves day to day needs a trend before it means anything at all.
greg_boulder 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…
Pushing back on greg_boulder 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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Shop Reference StandardsAnswering the narrow version, because the broad one does not have a single answer. 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.
Ask again with the specifics and you will get a better answer than this one.
TrialNerd_Beth said:Agreed, and one caution: a single measurement is not a measurement.
This matches mine closely enough to be worth saying so out loud.