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c/retatrutide·posted 2 years ago by u/dead_space_doug

someone explain phase 2 to me like I have not read a paper in years

Discussion Cold Box ×8 Sourced ×3 Receipts ×3

Genuine question, and the title is the question: someone explain phase 2 to me like I have not read a paper in years.

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

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

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

Not medical advice, obviously, and nothing here is approved for human use. One person with a spreadsheet.

7,930 up / 790 down91% upvoted34 commentsid eutie325 May 2024

34 comments

30 in this archive, depth 5

best — the order this archive was captured in

u/priya_weiss419 points·2 years 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/dead_space_dougOP304 points·2 years ago

the glucagon component is why the metabolic story reads differently

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u/andres_sorensen172 points·2 years ago

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

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u/isabela_nilsen-22 points·2 years ago

dose escalation in the trials was slow for a reason

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u/yara_lindholm1 point·2 years ago

Sent a vial to VendorInvestigate out of curiosity. Result was 99.1% against a claimed 98.5%, which is the first independent number I had seen for this compound anywhere.

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u/baseline_drifteranalytical1 point·2 years ago

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

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u/soren_nkemelu1 point·2 years ago

Sent a vial to VendorInvestigate out of curiosity.

yara_lindholm is right about the escalation being the variable. It explains most of the difficult reports here.

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u/mateusz_mensah463 points·2 years 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/careful_gradient_again108 points·2 years ago

the escalation is where most of the reported trouble sits

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u/ledger_modmod · vetting253 points·2 years 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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[removed]349 points·2 years ago

[removed by moderator]

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u/niels_lindqvist95 points·2 years 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_mbeki297 points·2 years ago·edited

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/elodie_grimaldi72 points·2 years ago

wait for phase 3 before you argue about rankings

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u/nordic_pricing51 points·2 years ago

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

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u/baseline_drifteranalytical41 points·2 years ago

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

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u/sena_teixeira101 points·2 years 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/lina_bruun157 points·2 years ago·edited

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/trialwatch_theotrial nerd124 points·2 years 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/signe_villalobos59 points·2 years ago

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

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u/blunt_coldbox_202445 points·2 years 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/sena_teixeira13 points·2 years 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/ewan_marchand4 points·2 years ago

a lot of the confident posting here is extrapolation

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u/dead_space_dougOP18 points·2 years ago

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.

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u/dead_space_dougOP36 points·2 years ago

Has anyone posted an independent test on this compound recently?

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u/marta_vanhecke28 points·2 years ago

the energy-expenditure story is mechanistically interesting and clinically unproven

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u/bilal_osei56 points·2 years ago·edited

triple agonist — GLP-1, GIP and glucagon, and the glucagon arm is the new part

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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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