Watching the glucagon co-agonists for the liver endpoints and finding almost nothing written about them that is not a press release.
The narrow version of the question 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 have searched first, so if this is covered somewhere point me at it and I will read it.
Short answer first, then the reasoning. 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.
mike_nyc said:Relative and absolute effects need reading together.
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.
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Browse GL Biochemrobert_kc said:Watching the glucagon co-agonists for the liver endpoints and finding almost nothing written about them that is not a press release.
Mine went the same way, slower.
From the other side of the consultation, briefly.
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].