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ForumsDosing & ProtocolsPK/PD modeling for tirzepatide — receptor occupancy calculations Page 2

PK/PD modeling for tirzepatide — receptor occupancy calculations

SarahChen_PharmD Mon, Feb 16, 2026 at 11:20 PM 12 replies 453 viewsPage 2 of 3
fiona_glasgow
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Feb 17, 2026 at 2:10 AM#6

For what it's worth, there was a retrospective analysis (Rubino et al., presented at ObesityWeek 2024) looking at patients who switched from semaglutide to tirzepatide. The cohort that did accelerated titration (2wk/2wk through starter doses) had comparable GI adverse event rates to the standard titration group. N was small though (~180 patients).

The more interesting finding was that 73% of sema "plateau" patients resumed weight loss within 8 weeks of reaching tirz 7.5mg or higher.

36 8TrialTracker_MD, JennaRN, LabKate and 33 others
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Dr.NephBHM_UK
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Feb 17, 2026 at 2:27 AM#7

following this thread! im in the exact same boat. stalled on wegovy 2.4 for almost 4 months now 😩

Last edited: Feb 17, 2026 at 8:27 AM
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FDA_TrackerJim
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Feb 17, 2026 at 2:44 AM#8
fiona_glasgow said:
For what it's worth, there was a retrospective analysis (Rubino et al., presented at ObesityWeek 2024) looking at patien...

73% resumed weight loss — that tracks with what I've seen anecdotally on here and on the Discord. The other 27% probably needed 10mg+. Have you seen any data on what happens to that remaining group at higher tirz doses?

Last edited: Feb 17, 2026 at 5:44 AM
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DebRD_ATL
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Feb 17, 2026 at 3:01 AM#9

UPDATE — Week 2:

Ok so I'm finishing my second week on 2.5mg and here's what I'm noticing:

  • Appetite suppression is milder than what I had on Wegovy, but it's... different? Hard to explain but food doesn't look as "exciting" if that makes sense
  • Zero nausea so far (I had horrible nausea on sema for the first 2 months)
  • Energy is UP. Like noticeably. I thought people were exaggerating about the tirz energy boost but no, it's real
  • Down 2.1 lbs already after 4 months of nothing on sema
  • No sulfur burps yet 🤞

Moving to 5mg next week per my endo's accelerated plan. Will keep updating!

SW: 247 | CW: 206.9 | GW: 165

Last edited: Feb 17, 2026 at 7:01 AM
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Dr.PathRoch
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Feb 17, 2026 at 3:18 AM#10

The energy increase you're describing is something I hear from probably 60% of my patients who switch. There's some mechanistic basis for it — GIP receptor activation in the brain may have distinct effects on perceived energy vs pure GLP-1 agonism. It's not well studied yet but it's a very consistent patient-reported outcome.

Glad the transition is going smoothly! 🙌

36 9Dr.MetabolicMD, RetaRick_CA, JenPlateau and 33 others
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