small win: dose escalation stopped being a problem at week 55
small win: dose escalation stopped being a problem at week 55, logged the same way every week so the comparison is at least internally fair.
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.
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.
Happy to answer the boring questions. Those are usually the ones worth asking.
best — the order this archive was captured in
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.
Cosigning the escalation point. Almost every difficult report on this board is from somebody who went up quickly.
Phase 2 estimates effect and finds a dose range.
Agreed, and the glucagon arm is exactly why the comparison threads do not work.
Which phase 2 arm are you quoting, and at what week?
Yes — the comparison threads are apples to oranges and they generate more heat than anything else here.
That is body weight change, not fat mass. The trials report the first and people quote it as the second.
Sceptical of the extrapolation. Forty-eight weeks does not tell you about seventy-two, and the curve shape is exactly what is unknown.
Trial names corrected in the title. The phase 3 programme and the phase 2 readout are not the same thing.
research-use-only material is not approved for human use, full stop
research-use-only material is not approved for human use, full stop
Disagree with this specific inference. A 48-week readout does not tell you the shape of the curve after it.
Has anyone posted an independent test on this compound recently?
Watched heart rate on a wearable across twelve weeks because the threads said to. It moved a little and I have no idea whether that means anything.
How fast was the escalation? That is usually the variable that explains the reports.
How fast was the escalation?
This is the sentence the rest of the board should read first. Phase 2 is not a label.
Right, and it bears repeating that nothing here is approved anywhere and research material is not for human use.
Agreed, and the framing that helps is: this is a phase 2 compound with phase 3 running. Everything else is inference.
Agreed, and the framing that helps is: this is a phase 2 compound with phase 3 running.
Adding the standing caveat: none of this is approved anywhere and research material is not for human use.
What do you think the glucagon component is adding, specifically?
the escalation is where most of the reported trouble sits
The thing that surprised me was how much of the discussion here is inference rather than measurement.
Disagree. "More receptors means more effect" is not how any of this works and the trial data does not support the linear story.
Glucagon receptor agonism is associated with increased energy expenditure and with hepatic effects. That is a mechanistic story with strong preclinical support and limited phase 2 human data.
Not convinced. You are attributing a week of muscle cramps to the glucagon arm when the escalation rate alone would explain it.
wait for phase 3 before you argue about rankings
the phase 2 numbers were striking and they were also 48 weeks in a small population
comparing reta phase 2 to sema phase 3 is comparing different things
- 1Yes — the comparison threads are apples to oranges and they generate more…8 comments in this branch · started by u/halima_mbeki