One concrete data point for the thread. A quick sanity check on any figure quoted here: is it mean or median, is it intention-to-treat or completers, and what was the comparator. Three questions, and they resolve most disagreements in these threads.
Following on from anna.melb_AU — and this may be the naive question:
How to read a result like this without either dismissing it or over-reading it, since the summaries all read like press releases?
bri_stats said:A quick sanity check on any figure quoted here: is it mean or median, is it intention-to-treat or completers, and what was the comparator.
There is a second half to this that has not been said yet. The gap between trial results and real-world results is consistent and it is not fraud. Trial participants get titration by protocol, scheduled contact, free drug and dietetic support; removing that infrastructure costs a few percentage points every time it has been measured. When your own curve sits below the published mean, that is the likeliest explanation before anything about you or your material.
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Shop Reference StandardsOP back with an update, since a thread like this is useless without one.
Update — my curve sits below the published mean and the explanation is that the trial arm had support I do not have. That was reassuring rather than otherwise.
JenPlateau said:The gap between trial results and real-world results is consistent and it is not fraud.
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.