Journal club: SURPASS-2 and the semaglutide 1 mg comparator

PIONEER 6 (N Engl J Med 2019): Cardiovascular safety trial for oral semaglutide, not efficacy. Non-inferiority for safety was met. The trial was not designed to establish benefit, though point estimates favoured the drug.

Two people in this thread mean different things by SURPASS-2 and are disagreeing about the definition while believing they are disagreeing about the facts. Worth pausing to define it.

That is clearer than the version I had in my head. Thank you.

Where I part company with post #29, and it is a narrow parting.

The useful distinction on SURPASS-2 is between what was measured and what was inferred from it. Both end up in the same sentence and only one of them has error bars.

Post #33 put the caveat in the right place and I want to underline it.

Sessions on negative or null results are consistently the most instructive and the hardest to get anyone to attend.

This is the sort of thing the wiki should carry and currently does not.

SOUL (N Engl J Med 2025): Oral semaglutide cardiovascular outcomes. Extends the cardiovascular evidence to the oral formulation. Note that oral bioavailability is lower and more variable than injectable.

I have deliberately not rounded that, because the rounding is where the argument starts.

STEP 1 (N Engl J Med 2021): The pivotal obesity trial for semaglutide and the reference point for most subsequent comparison. Mean weight reduction was substantially larger than anything previously achieved pharmacologically.

That is consistent with mine, for whatever one more account is worth.