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ForumsRetatrutide & Triple AgonistsRetatrutide mechanism: GLP-1/GIP/glucagon triple agonism explained — looking for input Page 2

Retatrutide mechanism: GLP-1/GIP/glucagon triple agonism explained — looking for input

wendy_avl Tue, Sep 24, 2024 at 8:59 AM 13 replies 1,809 viewsPage 2 of 3
greg_boulder
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Jul 2024
Boulder, CO
Sep 24, 2024 at 5:06 PM#6

Sorry if this is a dumb question but how is this different from tirzepatide? I thought Mounjaro was already the "best" option. Now there's something even better? How long until insurance would cover this?

Last edited: Sep 24, 2024 at 7:06 PM
3 23denise_HTX, raj_cambridge, ingrid_STO
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LibrarianMeg
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Mar 2024
Baltimore, MD
Sep 24, 2024 at 8:18 PM#7

Not a dumb question at all. The key difference is the third receptor:

  • Semaglutide = GLP-1 agonist (one receptor)
  • Tirzepatide = GLP-1 + GIP agonist (two receptors)
  • Retatrutide = GLP-1 + GIP + glucagon agonist (three receptors)

The glucagon component is theorized to increase energy expenditure (thermogenesis) and promote hepatic fat oxidation. So you're not just reducing appetite — you're also potentially burning more calories at rest. That's the mechanistic hypothesis for the superior efficacy.

As for insurance: Lilly hasn't filed yet. Optimistic timeline is FDA approval late 2026, commercial launch early 2027. Insurance coverage usually lags 6-12 months after that, depending on the payor.

2 22PharmD_Rodriguez, julia.endo
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BenResearch_OR
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Dec 2023
Oregon
Sep 24, 2024 at 11:30 PM#8

One thing that isn't getting enough attention: the TRIUMPH-4 trial is studying retatrutide specifically for MASH (metabolic-associated steatohepatitis). The Phase 2 liver fat data was remarkable — something like 80%+ of participants achieved ≥70% liver fat reduction. If that holds up in Phase 3, retatrutide could be approved for both obesity AND liver disease, which would be a first for any incretin.

This is the drug I'm most excited about in the pipeline, full stop.

1 21Dr.NateNeph
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