Following the glucagon co-agonists mostly for the liver endpoints rather than the weight ones, which seems to be the opposite of how they get discussed here.
The question I want answered 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.
I would rather have one careful answer than five confident ones.
LeilaHI said:Following the glucagon co-agonists mostly for the liver endpoints rather than the weight ones, which seems to be the opposite of how they get…
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.
PharmD_Rodriguez said:Glucagon receptor pharmacology in triple agonists (retatrutide), relevant to the glucagon co-agonists: the glucagon component is the most…
Correct, and worth adding that it is reversible. Nothing being described here is a one-way door, which changes how cautious it is reasonable to be.
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View ResultsLeilaHI said:Following the glucagon co-agonists mostly for the liver endpoints rather than the weight ones, which seems to be the opposite of how they get…
Same pattern here, and in the same order. Nothing to add that would improve it.
Adding the clinical framing, because it changes how the question reads. Start from the measurement rather than the conclusion. Almost every disagreement here turns out to be two people measuring different things and comparing the numbers anyway.