This gets cited here weekly, usually second-hand, so it is worth setting out what it does and does not establish.
The liver data is among the strongest non-weight findings in the class. The semaglutide MASH programme reported a large advantage over placebo on MASH resolution, with a substantial minority also achieving fibrosis improvement — and fibrosis is the endpoint that predicts outcomes. Mechanistically it is reduced hepatic lipogenesis, increased fatty-acid oxidation, less hepatic inflammation, and possibly a direct effect on stellate-cell activation.
Where I think it is weakest: the completion rate deserves as much attention as the headline, because a large effect among those who finished is a different claim from a large effect among those enrolled.
What would genuinely help is knowing whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. I would rather have one careful answer than five confident ones.
MASHdoc_SA said:The liver data is among the strongest non-weight findings in the class.
Agreed, and subgroup analyses deserve particular suspicion. With enough subgroups something is significant by chance, and pre-registered subgroups are a different animal from ones found afterwards.
MASHdoc_SA said:The liver data is among the strongest non-weight findings in the class.
I read this differently from MASHdoc_SA, on substance rather than tone. I would add the less popular caveat: these trial populations under-represented several groups, older adults and the highest BMI categories among them. The results probably generalise, and "probably" should be stated as an assumption rather than dropped.
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View ResultsShort answer first, then the reasoning. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.
If somebody has the primary source to hand I would rather cite it than paraphrase it.
TrialNerd_Beth said:Agreed, and subgroup analyses deserve particular suspicion.
Second this. The detail I would add is minor and it is already implied above.