PIONEER 6 cardiovascular safety, read as a safety trial rather than an efficacy one — does this still hold?

On post #2 — agreed on the reasoning, with one qualification.

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.

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.

PIONEER programme is phase 3 for oral semaglutide. The trials cover multiple indications and durations. Reading them requires attention to which trial is which because they are not all the same question.

post #22 is right about the mechanism and I think understates the practical bit.

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.

Coming back to post #24, because the follow-up matters more than the original answer.

Why an oral formulation is a formulation achievement: the molecule is the same but the tablet is novel. Getting a peptide across the gastric epithelium at usable bioavailability is a chemistry problem, not a dose problem.