Putting this up for argument rather than for agreement. I have read it twice and I am still not certain what it supports.
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 follow-up is short relative to how long people actually take these drugs, so durability is an assumption here rather than a finding.
What I am after is 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. Tell me what I have not thought of.
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.
Worth saying that the confident version of this is more useful to the person writing it than to the person reading it.
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View ResultsThis one has a reasonably settled answer, so here it is. The useful move here is to separate what is established from what is widely repeated. Those two sets overlap less than the confident tone of most write-ups suggests, and the second set is where nearly all the disagreement on this board comes from.
SarahChen_PharmD said:Glucagon receptor pharmacology in triple agonists (retatrutide), relevant to the glucagon co-agonists: the glucagon component is the most…
This is my experience too, for whatever a second data point is worth. Posting only so the count is not one.