[Discussion] can we stop arguing about dose escalation until somebody posts a number
can we stop arguing about dose escalation until somebody posts a number. Searched first, found three threads that contradict each other, hence the post.
Went up slowly, deliberately, because everything on this board says the escalation is where trouble lives. Uneventful so far and I am not going to pretend that is a finding.
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.
Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.
best — the order this archive was captured in
Left up. It reads the phase 2 paper carefully and it is honest about the intervals.
[removed by moderator]
Correction: TRIUMPH is the phase 3 programme. The number you are quoting is from the phase 2 readout, which is a different trial.
research-use-only material is not approved for human use, full stop
The phase 2 readout ran to 48 weeks in a few hundred participants with a slow escalation. Both the size and the duration matter when people quote the headline number.
Independent purity testing on this compound is thin compared with the older molecules, simply because fewer members have paid for it. Fewer results means wider uncertainty, not a verdict.
That reads as a titration plan for an unapproved compound. This board cannot host that and it should not want to.
a lot of the confident posting here is extrapolation
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.
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.
small trial, big effect, wide error bars
That reads as a titration plan for an unapproved compound.
heart_rate_bump is right about the escalation being the variable. It explains most of the difficult reports here.
the phase 2 numbers were striking and they were also 48 weeks in a small population
wait for phase 3 before you argue about rankings
Careful with the rankings. A phase 2 result and a phase 3 result are not on the same evidential footing and cannot be listed in one table.
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.
Small fix — three receptors, not two. GLP-1, GIP and glucagon, and the third one is the reason this compound gets its own board.
the energy-expenditure story is mechanistically interesting and clinically unproven
Not convinced. You are attributing a week of sulphur burps to the glucagon arm when the escalation rate alone would explain it.
Correcting my own comment above: that figure was the 36-week interim, not the 48-week endpoint.
heart rate is the thing people report watching
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.
dose escalation in the trials was slow for a reason
That is body weight change, not fat mass. The trials report the first and people quote it as the second.
That is body weight change, not fat mass.
Agreed, and the glucagon arm is exactly why the comparison threads do not work.
- 1That reads as a titration plan for an unapproved compound. This board cannot…8 comments in this branch · started by u/heart_rate_bump
- 2Increases in heart rate have been reported across this receptor class. The…6 comments in this branch · started by u/mod_cold_room