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

dose escalation — my 16-week log, condensed into one table

Question Clean Column ×4 Sourced ×3 Long Haul ×2

The title is the argument: dose escalation — my 16-week log, condensed into one table. Here is the rest of it.

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.

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.

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.

Happy to answer the boring questions. Those are usually the ones worth asking.

9,695 up / 3,680 down72% upvoted68 commentsid 1eicxz25 Apr 2025

68 comments

30 in this archive, depth 4

best — the order this archive was captured in

u/niels_lindqvist930 points·1 year ago

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.

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u/reta_and_regretMOD490 points·1 year ago

Trial names corrected in the title. The phase 3 programme and the phase 2 readout are not the same thing.

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u/deleted_my_history215 points·1 year ago

research-use-only material is not approved for human use, full stop

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[removed]338 points·1 year ago

[removed by moderator]

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u/niels_lindqvist-29 points·1 year ago

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.

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u/nausea_notesside effects1 point·1 year ago·edited

That is body weight change, not fat mass. The trials report the first and people quote it as the second.

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u/tired_ledger_notes446 points·1 year ago

the phase 2 numbers were striking and they were also 48 weeks in a small population

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u/hassan_nilsen283 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/lina_bruun128 points·1 year ago

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/zeynep_mbeki217 points·1 year ago

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

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u/farid_molnar211 points·1 year ago

How fast was the escalation? That is usually the variable that explains the reports.

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u/crosspost_bot_no112 points·1 year ago

What do you think the glucagon component is adding, specifically?

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u/renzo_yildiz34 points·1 year ago

wait for phase 3 before you argue about rankings

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u/hugo_pires184 points·1 year ago

the TRIUMPH programme is still running, so anything definitive is premature

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u/ferran_krastev269 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/blunt_coldbox_202460 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/cold_chromatogram_only0 points·1 year ago

the TRIUMPH programme is still running, so anything definitive is premature

Disagree with this specific inference. A 48-week readout does not tell you the shape of the curve after it.

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u/honest_syringe331 point·1 year ago

the glucagon component is why the metabolic story reads differently

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u/placebo_arm_pam110 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/yannick_salinas59 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/niels_lindqvist40 points·1 year ago

Small fix — three receptors, not two. GLP-1, GIP and glucagon, and the third one is the reason this compound gets its own board.

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u/incretin_ivypharmacology25 points·1 year ago

Are you tracking heart rate at all?

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u/lina_bruun7 points·1 year ago

dose escalation in the trials was slow for a reason

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u/renzo_yildiz56 points·1 year ago·edited

comparing reta phase 2 to sema phase 3 is comparing different things

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u/rekha_vestergaard31 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/liver_enzyme_liz26 points·1 year ago

heart rate is the thing people report watching

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u/employer_carveout45 points·1 year ago

the energy-expenditure story is mechanistically interesting and clinically unproven

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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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