Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using 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.
What would genuinely help is knowing 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.
TrialTracker_MD said:The glucagon co-agonists — survodutide, mazdutide, ecnoglutide — are all chasing the same idea: add energy expenditure to appetite suppression.
Glucagon receptor pharmacology in triple agonists (retatrutide), relevant to the glucagon co-agonists: the glucagon component is the most controversial because glucagon traditionally raises blood glucose. So why include it in an anti-obesity drug?
Key insight: glucagon increases energy expenditure (thermogenesis), promotes hepatic lipid oxidation, and reduces appetite through distinct CNS mechanisms. The hyperglycemic effect is counterbalanced by the GLP-1 component's insulin secretagogue action.
Net result: more weight loss through increased expenditure (glucagon) + decreased intake (GLP-1/GIP), with neutral or improved glycemia. An elegant pharmacological balancing act[1].
[1] Day JW, et al. Nat Rev Drug Discov. 2022;21:37-54.
TrialTracker_MD said:The glucagon co-agonists — survodutide, mazdutide, ecnoglutide — are all chasing the same idea: add energy expenditure to appetite suppression.
Pushing back on TrialTracker_MD here. Pushing back on the anecdote-stacking. Twenty people reporting the same thing is twenty samples from the same self-selected pool, not twenty independent confirmations.
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Shop Reference StandardsShort answer first, then the reasoning. There is a difference between no evidence and evidence of no effect, and this subject is one where the two get swapped freely in both directions.
Dr.PainCLE said:Glucagon receptor pharmacology in triple agonists (retatrutide), relevant to the glucagon co-agonists: the glucagon component is the most…
Same experience, arrived at from the opposite direction. I had assumed I was the exception until I read this.