[Paper] survodutide MASH data is the most interesting hepatic readout in the class
The phase 2 MASH results (NEJM, 2024) are, to me, the most underdiscussed thing in this whole space.
Biopsy-confirmed endpoints. Not an ALT screenshot, not imaging, actual histology. That is a much higher evidentiary bar than most of what gets argued about here, and the response rates were substantial.
My own ALT went 34 to 19 over seven months on a different drug entirely and I have been careful never to present that as evidence of anything. This is what evidence looks like instead.
best — the order this archive was captured in
Glucagon receptor co-agonism has a plausible hepatic mechanism, which is why this is a mechanistically satisfying result rather than a surprising one. Increased hepatic fat oxidation and energy expenditure are the usual explanation offered.
The thing I would flag: glucagon co-agonism also has its own safety considerations, and generalising tolerability from tirzepatide — where the second receptor is GIP, not glucagon — is a mistake this community makes constantly.
agreed, and it is in the community rules for exactly that reason. two dual agonists, two completely different second receptors.
and the HR signal on the glucagon-containing molecules is worth tracking properly rather than anecdotally. mine went up 7bpm on titration on a triple agonist and back down at maintenance.
a resting HR increase of a few bpm is a consistent class finding and it has not translated into a cardiovascular harm signal in the outcome trials we have. those two facts sit together uncomfortably and both are true.
which is a good example of why a surrogate moving in a worrying direction is not an outcome. SELECT is the reason we can say that with any confidence at all.
Correct flair, correct bar for a hepatic claim. This community requires biopsy data for MASH claims and this is why — imaging and enzymes are proxies and the proxies disagree with histology often enough to matter.
the parallel with the renal endpoints is worth drawing. both are cases where the hard endpoint is expensive and the cheap proxy is noisy at the individual level.
my hs-CRP halved before the scale moved much, which is the sort of observation i have learned to file as "interesting to me, evidence of nothing". edit: this thread is a good model for that distinction.
phase 2 hepatic data in a small population is not "the most interesting readout in the class"
on evidentiary quality per participant, biopsy endpoints beat almost everything else in the class. on size, you are right. those are different rankings and i should have said which one i meant.
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