glucagon: what the trials say vs what this community says
glucagon: what the trials say vs what this community says, and I am aware this is a minority view on this board.
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.
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.
The standing caveat, written out properly because it keeps getting compressed into a footnote.
Nothing containing this compound is approved by any regulator. Research-use-only material is not approved for human use. That is not a legal formality on this board — it is why there is so little independent data, why the escalation schedules people post are invented, and why nobody here can answer a dosing question.
What this board can usefully do is read the published trials carefully, log independent purity results, and be honest about how thin the evidence base is. Everything else belongs somewhere with a clinician in it.
That is everything I have. The rest is opinion and I have tried to keep it out.
best — the order this archive was captured in
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.
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.
comparing reta phase 2 to sema phase 3 is comparing different things
Trial names corrected in the title. The phase 3 programme and the phase 2 readout are not the same thing.
Which phase 2 arm are you quoting, and at what week?
That is body weight change, not fat mass. The trials report the first and people quote it as the second.
Disagree. "More receptors means more effect" is not how any of this works and the trial data does not support the linear story.
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.
That reads as a titration plan for an unapproved compound. This board cannot host that and it should not want to.
Push back: quoting the phase 2 headline as an expected outcome is not a fair reading of a small trial with wide intervals.
Stopped at a low step because there was no reason to go further and no data to tell me what further would do.
the escalation is where most of the reported trouble sits
Agreed, and the framing that helps is: this is a phase 2 compound with phase 3 running. Everything else is inference.
the energy-expenditure story is mechanistically interesting and clinically unproven
Small fix — three receptors, not two. GLP-1, GIP and glucagon, and the third one is the reason this compound gets its own 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.
small trial, big effect, wide error bars
heart rate is the thing people report watching
small trial, big effect, wide error bars
Disagree with this specific inference. A 48-week readout does not tell you the shape of the curve after it.
the phase 2 numbers were striking and they were also 48 weeks in a small population
the phase 2 numbers were striking and they were also 48 weeks in a small population
Agreed, and the glucagon arm is exactly why the comparison threads do not work.
The reflux profile felt different rather than worse. Hard to describe and impossible to quantify, so take it as an impression.
not approved anywhere, which is the single most important fact in this board
- 1Increases in heart rate have been reported across this receptor class. The…8 comments in this branch · started by u/ewan_marchand
- 2The phase 2 readout ran to 48 weeks in a few hundred participants with a…7 comments in this branch · started by u/matias_falk