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Evidence-based GLP-1 & peptide discussion since 2023
ForumsRetatrutide & Triple AgonistsWill retatrutide be the first to break 25% weight loss in Phase 3? — what worked for you? Page 2

Will retatrutide be the first to break 25% weight loss in Phase 3? — what worked for you?

LindaRN_retired Sat, Nov 16, 2024 at 7:55 PM 12 replies 1,790 viewsPage 2 of 3
DerekSJ_a1c
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San Jose, CA
Nov 16, 2024 at 10:45 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: Nov 17, 2024 at 3:45 AM
22 7adam_van, Dr.SurgeonPGH, rachel_ABQ and 19 others
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Dr.PeteFamMed
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Minneapolis, MN
Nov 16, 2024 at 11:02 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.

5 22tommy_boulder, hyun_seoul, jim_asheville and 2 others
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InsuranceTom
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Connecticut
Nov 16, 2024 at 11:19 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.

23 10Dr.ReproEndo, lucas_SP_BR, lisa_labSD and 20 others
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