retatrutide vs tirzepatide, one is approved and one isn't, why do people compare them like peers?

TripleAgonistWatchSenior Analyst

This comparison gets made constantly and the single most important fact usually gets buried.

Tirzepatide is approved for specific indications and has completed phase 3.

Retatrutide is investigational. Not through phase 3, not approved anywhere, for anything.

Mechanistically reta adds glucagon receptor agonism to the GLP-1/GIP combo, so it's a triple agonist. The glucagon part is counterintuitive (glucagon raises blood sugar) but the proposed rationale is energy expenditure rather than glycemic control alone.

The phase 2 results got a lot of attention and the reported weight reduction was large. Two things that matter enormously:

1. Phase 2 results routinely attenuate in phase 3. Bigger, longer, messier populations. This happens over and over and is the norm, not the exception. 2. Safety signals emerge with scale. A phase 2 population isn't big enough to characterize uncommon events.

Comparing them as if they were peers is the mistake I see most.

13 replies18 upvotesGLP-1 & Metabolic

Peptides discussed

13 replies

  • approved_vs_notSenior Analyst

    Thank you for leading with the status difference instead of burying it. The pattern I see is people quoting a phase 2 percentage next to tirzepatide's phase 3 number as if those are the same kind of measurement.

    10 upvotes

  • same_tbhSenior Analyst

    phase 2 is not phase 3. people need to hear it

    4 upvotes

  • PhaseTwoWatcherAnalyst

    Attenuation is routine and the reasons are structural. Broader inclusion, longer follow up, more sites. A phase 2 headline is a hypothesis about phase 3, not a preview of it.

    7 upvotes

  • unconvinced_stillSenior Analyst

    Also worth remembering how many things looked great at phase 2 and never made it. Survivorship bias is severe here.

    6 upvotes

    • TripleAgonistWatchSenior Analyst

      And the glucagon receptor specifically has a history of programs not making it.

      4 upvotes

  • quick_qSenior Analyst

    whats the actual phase 2 number everyone quotes?

    1 upvote

  • MetabolicLurkerSenior Analyst

    how far off is the phase 3 readout roughly?

    3 upvotes

    • RegistryWatcherSenior Analyst

      Check the registry directly rather than trusting a forum post. Completion estimates move. Rather point you at the source than give you a number that ages badly.

      6 upvotes

  • deload_weekAnalyst

    reta hype is unreal rn

    3 upvotes

  • GIsideeffectsSenior Analyst

    The discontinuation rates in the escalation arms tell you something the efficacy headline doesn't.

    4 upvotes

  • newvialwhodisSenior Analyst

    phase 3 when?

    2 upvotes

  • amylin_nextAnalyst

    Slightly off topic but the amylin combinations are what I'd watch alongside this.

    3 upvotes

  • hype_cycle_watchAnalyst

    reta is near peak hype rn which is exactly when the caveats in this post land worst. someone repost it after the readout

    5 upvotes

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