Compounds · Oral incretins · continued

Why oral semaglutide needs an absorption enhancer at all posts 61–66

Compounds › Oral incretins randomised trial orforglipron oral semaglutide SOUL trial Solved

This is a continuation of a long topic, addressed by post number rather than by page. Start at post 1 · go to the accepted answer.

k.vanheckeTL2 Moderator24 Dec 2025#61

h.hutchings, post #26: Trial adherence in an oral trial with strict administration requirements is genuinely worse than trial-published data often suggests. That is why the exposure variability in oral formulations is mentioned repeatedly in the discussions here. Go to post

Orforglipron is a small molecule, not a peptide. That changes almost everything: no absorption enhancer required, no fasting window, chemical synthesis instead of peptide synthesis, different analytical methods entirely. Data from peptide agonists does not transfer.

7 likes in reply to #26 7mo

k.fonsecaTL227 Dec 2025#62

Collapsed as off-topic by two members at trust level 3 or above

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

bench_notesTL4 Moderator30 Dec 2025#63

Staff post. Actions described here are recorded in the public moderation log and may be challenged in Meta.

Oral versus injectable exposure: comparing a 14 mg oral dose with a 0.5 mg injectable dose is comparing apples to a different fruit. The oral bioavailability is low enough that dose numbers are an order of magnitude different and not directly comparable.

0 likes 7mo

v.baptistaTL2 Moderator3 Jan 2026#64

f.haddad, post #41: PIONEER 6 was a cardiovascular safety trial for oral semaglutide, not an efficacy trial. Non-inferiority for safety was demonstrated. The point estimates favoured the drug but the trial was not designed to establish benefit. Go to post

This follows post #61 rather than contradicting it.

Dose numbers for oral formulations are not comparable to injectable ones. The 14 mg oral dose is not equivalent to any injectable dose in the traditional comparison sense. They are different formulations with different pharmacokinetics and cannot be put on the same scale.

24 likes in reply to #41 7mo

PharmNotes_WhitfieldTL4Pharmacist6 Jan 2026#65

On post #61 — agreed on the reasoning, with one qualification.

Having read the exchange above, I think I was wrong earlier in this topic and I want to say so plainly rather than quietly editing.

The correction was fair and I had been repeating something I had not checked carefully enough.

3 likes 7mo

a.vukovicTL2 Moderator9 Jan 2026#66

The SOUL trial: cardiovascular outcomes trial for oral semaglutide in people with type 2 diabetes and cardiovascular disease or chronic kidney disease. It demonstrates that benefit appears to be a property of the molecule and exposure, not specific to the route.

0 likes 7mo

This topic was referenced in

Oral versus injectable exposure: comparing apples to a different fruitCompounds › Oral incretins · 23 replies

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