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 subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
The bit I cannot resolve on my own 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.
TrialTracker_MD said:The manufacturing argument is the underrated one.
Agreed, with the qualification that SELECT enrolled a secondary-prevention population. Extrapolating a 20% relative reduction to a healthy 35-year-old with a BMI of 31 is not what that trial showed.
TrialTracker_MD 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.
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View ResultsTaking the question as asked, rather than the general version of 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.
Happy to go further on any of that.
DebRD_ATL said:Agreed, with the qualification that SELECT enrolled a secondary-prevention population.
Mine went the same way, slower. I had assumed I was the exception until I read this.