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ForumsRetatrutide & Triple AgonistsGlucagon-mediated thermogenesis on retatrutide — looking for input Page 2

Glucagon-mediated thermogenesis on retatrutide — looking for input

SkepticalSean Sat, Jun 14, 2025 at 8:51 AM 17 replies 1,657 viewsPage 2 of 4
wendy_avl
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Oct 2024
Asheville, NC
Jun 14, 2025 at 11:41 AM#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?

30 20SleepFixSam, PurityPaulOR, MaxMetOK and 27 others
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Dr.NephBHM_UK
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Jun 2024
Birmingham, UK
Jun 14, 2025 at 11:58 AM#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.

30 10EndoResFellow, PharmacoVig_BOS, SurmountFan_IN and 27 others
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DanielChem_CHI
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Chicago, IL
Jun 14, 2025 at 12:15 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.

38 23patPC_UT, Dr.DermMIA, fiona_VT and 35 others
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