[Discussion] dose-response looked steeper than anything else in the class and that cuts both ways
dose-response looked steeper than anything else in the class and that cuts both ways, and I am aware this is a minority view on this board.
Increases in heart rate have been reported across this receptor class. The magnitude and clinical significance are exactly what phase 3 is powered to establish.
Phase 2 estimates effect and finds a dose range. Phase 3 estimates it precisely in a bigger population and catches what phase 2 was too small to see. Treating them as the same tier of evidence is the recurring error here.
Nothing containing this compound is approved anywhere. Research-use-only material is not approved for human use, and that is a statement of fact rather than a disclaimer.
I will update this if the picture changes rather than quietly leaving it up.
best — the order this archive was captured in
It is a triple agonist at the GLP-1, GIP and glucagon receptors. The glucagon arm is the genuinely novel component and it is the one with the least human outcome data behind it.
Where the evidence actually stands, since every thread here assumes a different answer.
Phase 2 reported a large mean body weight change at 48 weeks across a few hundred participants with a slow, protocol-driven escalation. The effect size was striking. The confidence intervals were wide, the population was small, and the duration was under a year.
Phase 3 is running. Until it reports, everything else — including the ranking arguments this board loves — is extrapolation from a small study. That is not a criticism of the compound; it is a description of the evidence.
a lot of the confident posting here is extrapolation
Read the phase 2 paper twice before ordering anything. Recommend that to anyone in this board: the error bars are the interesting part.
What do you think the glucagon component is adding, specifically?
Push back: quoting the phase 2 headline as an expected outcome is not a fair reading of a small trial with wide intervals.
not approved anywhere, which is the single most important fact in this board
Yes — the comparison threads are apples to oranges and they generate more heat than anything else here.
Same read. The energy-expenditure mechanism is the interesting bit and it is not established in humans at scale.
Sent a vial to PeptideMeter out of curiosity. Result was 97.5% against a claimed 97.0%, which is the first independent number I had seen for this compound anywhere.
triple agonist — GLP-1, GIP and glucagon, and the glucagon arm is the new part
Is that the 48-week figure or an earlier readout?
What the glucagon arm is doing, as best anyone can say from public data.
GLP-1 and GIP agonism cover appetite and insulin secretion in ways that are now reasonably well characterised. Glucagon receptor agonism is the third leg and it is associated with increased energy expenditure and with effects on hepatic fat.
Mechanistically that is why this compound reads as a different proposition rather than a stronger version of a dual agonist. Clinically, the size and durability of that difference in humans is precisely what is not yet established, and anyone telling you otherwise is filling a gap with confidence.
That is body weight change, not fat mass. The trials report the first and people quote it as the second.
Not convinced. You are attributing a week of nausea to the glucagon arm when the escalation rate alone would explain it.
Are you comparing against phase 3 numbers for something else? They are not comparable.
Cosigning the escalation point. Almost every difficult report on this board is from somebody who went up quickly.
- 1What do you think the glucagon component is adding, specifically?7 comments in this branch · started by u/iman_castellanos