Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
What would genuinely help is knowing whether normalised enzymes tell you anything about fibrosis, and what the right follow-up measurement is. Numbers rather than impressions, if you have them.
BethLabQueen 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.
BethLabQueen said:The liver data is among the strongest non-weight findings in the class.
I read this differently from BethLabQueen, 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. The gap between trial results and real-world results is consistent and it is not fraud. Trial participants get titration by protocol, scheduled contact, free drug and dietetic support; removing that infrastructure costs a few percentage points every time it has been measured. When your own curve sits below the published mean, that is the likeliest explanation before anything about you or your material.
COA_Karl said:Agreed, and subgroup analyses deserve particular suspicion.
Adding a me-too, because a thread of one person's experience is not much use. The detail I would add is minor and it is already implied above.