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c/retatrutide·posted 1 year ago by u/yannick_barros

unpopular opinion: most of what gets said here about phase 2 is guesswork

Trial Data Cold Box ×5 Slow Clap ×1 Sourced ×1

unpopular opinion: most of what gets said here about phase 2 is guesswork. Change my mind, genuinely — I have no stake in being right about this.

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.

Stopped at a low step because there was no reason to go further and no data to tell me what further would do.

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.

Sceptical readings welcome. The confident ones are the ones I distrust.

20,076 up / 7,298 down73% upvoted33 commentsid 1ubyb513 Dec 2024

33 comments

26 in this archive, depth 6

best — the order this archive was captured in

u/rohan_cardoso-32 points·1 year ago

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.

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[removed]1 point·1 year ago

[removed by moderator]

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u/andres_restrepo1.3k points·1 year ago

This. The phase 2 result was genuinely large and it was also 48 weeks in a few hundred people.

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u/lina_bruun984 points·1 year ago

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.

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u/reta_and_regret1.4k points·1 year ago

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.

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u/lurker_for_years2k points·1 year ago

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.

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u/clara_weiss230 points·1 year ago

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.

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u/zeynep_mbeki515 points·1 year ago

Kept a log specifically because there is so little published. It is one person and it is not data.

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u/mod_cold_roommod · c/coldchain390 points·1 year ago

the glucagon component is why the metabolic story reads differently

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u/signe_villalobos386 points·1 year ago

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.

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u/divya_bakken179 points·1 year ago·edited

Agreed on the heart-rate reports. They are consistent enough across the threads to be worth noting, not enough to be a finding.

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u/titration_marshalmod · c/semaglutide193 points·1 year ago

That reads as a titration plan for an unapproved compound. This board cannot host that and it should not want to.

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u/kavya_kravchenko351 points·1 year ago

Disagree. "More receptors means more effect" is not how any of this works and the trial data does not support the linear story.

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u/bilal_osei93 points·1 year ago

Same read. The energy-expenditure mechanism is the interesting bit and it is not established in humans at scale.

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u/aa_analysis_andy184 points·1 year ago

The thing that surprised me was how much of the discussion here is inference rather than measurement.

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u/yannick_salinas150 points·1 year ago

heart rate is the thing people report watching

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u/yannick_barrosOP112 points·1 year ago

heart rate is the thing people report watching

Agreed, and the glucagon arm is exactly why the comparison threads do not work.

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u/yusuf_ramos91 points·1 year ago

the escalation is where most of the reported trouble sits

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u/iman_castellanos34 points·1 year ago

phase 2 data only, and people quote it like it is a label

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u/yannick_barrosOP0 points·1 year ago

Correcting my own comment above: that figure was the 36-week interim, not the 48-week endpoint.

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u/cold_chromatogram_only1 point·1 year ago

Cosigning the escalation point. Almost every difficult report on this board is from somebody who went up quickly.

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About c/retatrutide

Retatrutide: GIP/GLP-1/glucagon triple agonism, the TRIUMPH programme, and the fact that most people discussing it are handling research-grade material with no human-use approval anywhere. Dose-response, heart-rate signal, and the unusually steep phase-2 weight curves get argued about here weekly.

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