Read the primary source rather than the write-up and the two do not agree, so here is what is actually in it.
The glucagon co-agonists — survodutide, mazdutide, ecnoglutide — are all chasing the same idea: add energy expenditure to appetite suppression. The liver signal is where they look strongest, because hepatic fatty-acid oxidation responds to glucagon directly rather than as a consequence of weight loss.
Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.
So the question, as narrowly as I can put it: whether the liver signal is independent of weight loss or downstream of it, because that determines whether any of this is interesting for someone whose weight is already where they want it. Happy to be told the question itself is wrong.
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
TrialNerd_Beth said:The glucagon co-agonists — survodutide, mazdutide, ecnoglutide — are all chasing the same idea: add energy expenditure to appetite suppression.
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.
TrialNerd_Beth said:The glucagon co-agonists — survodutide, mazdutide, ecnoglutide — are all chasing the same idea: add energy expenditure to appetite suppression.
Pushing back on TrialNerd_Beth here. 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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Shop Reference StandardsAnswering the narrow version, because the broad one does not have a single answer. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.
LarryQC_SD said:Agreed, and subgroup analyses deserve particular suspicion.
Same pattern here, and in the same order.