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ForumsPublic SquareComparative pharmacokinetics: semaglutide vs tirzepatide vs retatrutide — need advice Page 3

Comparative pharmacokinetics: semaglutide vs tirzepatide vs retatrutide — need advice

emily_PDX Mon, Jul 22, 2024 at 4:07 PM 36 replies 2,470 viewsPage 3 of 8
DataDave
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Jul 23, 2024 at 4:26 AM#11
Dr.SleepRoch said:
Steady state is the thing most people miss.

That holds for the injectable. The oral formulation has different absorption behaviour and the dose numbers are not interchangeable, which is worth saying out loud because people quote them as if they were.

Last edited: Jul 23, 2024 at 5:26 AM
38 13VendorMark, COA_Karl, MikeFit_NJ and 35 others
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maya_sedona
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Jul 23, 2024 at 8:40 AM#12
Dr.SportsMedIN said:
The mechanism is more central than most summaries suggest.

This is exactly what I could not find anywhere else. I will report back once I have actually tried it.

37 12NurseAsh_DET, BenResearch_OR, MikeKY_noInsulin and 34 others
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maria_elpaso
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Jul 23, 2024 at 12:54 PM#13
Dr.SleepRoch said:
Steady state is the thing most people miss.

Filing a mild objection. Mild because I might be wrong; an objection because nobody has addressed the case that does not fit. The trial means are being read too generously in this thread. STEP populations were selected, supported, and titrated by protocol, and the real-world curves are consistently a few points worse. That difference is not noise, it is what happens when you remove the study infrastructure.

Last edited: Jul 23, 2024 at 6:54 PM
36 11TrialNerd_Beth, HPLC_Greg, LibrarianMeg and 33 others
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raj_cambridge
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Jul 23, 2024 at 5:08 PM#14
emily_PDX said:
Reading about receptor desensitisation and trying to work out which of the effects adapt over time and which do not, because people clearly experience…

Receptor pharmacology relevant to the pharmacology: semaglutide is a GLP-1R agonist with a C-18 fatty acid chain that enables albumin binding (>99%), creating a depot effect with a ~168-hour half-life enabling weekly dosing[1].

Tirzepatide is a dual GIP/GLP-1R agonist with higher GIP affinity (5:1 GIP:GLP-1 potency ratio). The GIP component may enhance beta-cell function and adipocyte lipid metabolism beyond what GLP-1 alone achieves.

For the pharmacology, the pharmacology explains the clinical differences between these agents.

References:
[1] Lau J, et al. J Med Chem. 2015;58(18):7370-7380.
Last edited: Jul 23, 2024 at 6:08 PM
35 10PharmHunterJen, TomTeleRx, DoseLogDan and 32 others
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mike_mod
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Jul 23, 2024 at 9:22 PM#15

Moderator note: good thread. Keeping it here rather than moving it, because the question is general enough to be useful. Thread quality here is what the rules are for. Keep it up.

34 9PurityPaulOR, MaxMetOK, MounjBrad and 31 others
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