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

small win: dose escalation stopped being a problem at week 19

Results Sourced ×3

small win: dose escalation stopped being a problem at week 19. This is a description of what happened to me and not a plan for anybody else.

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.

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.

Please do not ask me what dose you should be on. I genuinely do not know and neither does anyone else here.

878 up / 284 down76% upvoted19 commentsid 1ulxwu25 Dec 2024

19 comments

18 in this archive, depth 3

best — the order this archive was captured in

u/endotoxin_elliemicro85 points·1 year ago

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.

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u/solene_ilunga34 points·1 year ago

nothing here is available as a prescription product, so read every thread with that in mind

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u/careful_gradient3243 points·1 year ago

The standing caveat, written out properly because it keeps getting compressed into a footnote.

This is the sentence the rest of the board should read first. Phase 2 is not a label.

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[removed]62 points·1 year ago

[removed by moderator]

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u/careful_gradient_notes78 points·1 year ago

What is the source for that figure — the published paper or a summary of it?

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u/honest_syringe3359 points·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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u/mod_cold_roommod · c/coldchain-8 points·1 year ago

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.

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u/ismael_eriksen40 points·1 year ago

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.

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u/signe_villalobos11 points·1 year ago

Yes — the comparison threads are apples to oranges and they generate more heat than anything else here.

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u/discount_math_dm35 points·1 year ago

Read the phase 2 paper twice before ordering anything. Recommend that to anyone in this board: the error bars are the interesting part.

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u/cold_chromatogram_only28 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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u/bastian_ekstrom29 points·1 year ago·edited

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/nausea_notesside effects18 points·1 year ago·edited

Push back: quoting the phase 2 headline as an expected outcome is not a fair reading of a small trial with wide intervals.

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u/anya_moreau13 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/blunt_coldbox_202410 points·1 year ago·edited

The reflux profile felt different rather than worse. Hard to describe and impossible to quantify, so take it as an impression.

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u/yusuf_ramos3 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/solene_ilunga2 points·1 year ago

Right, and it bears repeating that nothing here is approved anywhere and research material is not for human use.

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u/two_mil_or_one2 points·1 year ago

Not convinced. You are attributing a week of early fullness to the glucagon arm when the escalation rate alone would explain it.

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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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