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ForumsPublic SquareComparative pharmacokinetics: semaglutide vs tirzepatide vs retatrutide — need advice Page 2

Comparative pharmacokinetics: semaglutide vs tirzepatide vs retatrutide — need advice

emily_PDX Mon, Jul 22, 2024 at 4:07 PM 36 replies 2,470 viewsPage 2 of 8
julia.endo
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Jul 22, 2024 at 6:08 PM#6
PurityPaulOR said:
The dose-response is real but shallow at the top.

I will push back on the "any working dose is fine" framing. The maintenance evidence sits overwhelmingly at the top studied dose, and the extension data shows regain tracking dose reduction rather than tracking stopping. Holding low is reasonable; pretending it is evidentially equivalent is not.

Worth separating that from semaglutide, which this thread keeps folding into the same question. They behave differently and the advice does not transfer.

30 8anna.melb_AU, mark_tokyo, hans_munich and 27 others
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stefan_berlin
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Jul 22, 2024 at 6:55 PM#7

One concrete data point for the thread. For anyone assembling their own picture: Tmax is one to three days, terminal half-life about 165 to 170 hours, steady state at four to five weeks, and subcutaneous bioavailability near 89%. Those four numbers explain most of the questions people ask about timing.

Last edited: Jul 22, 2024 at 9:55 PM
31 9JessicaH_TX, KevinCompounds, TirzTom and 28 others
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PedsEndoPhilly
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Jul 22, 2024 at 7:42 PM#8
julia.endo said:
I will push back on the "any working dose is fine" framing.

Coming at julia.endo’s question from a different direction. The mechanism that matters here is not stomach emptying, it is central. GLP-1 receptor agonism in the arcuate nucleus stimulates POMC neurons and suppresses AgRP/NPY signalling, which is why the effect is appetite and food salience rather than physical fullness. Delayed gastric emptying largely tachyphylaxes over the first months; the appetite effect does not.

32 10jason_paloalto, Dr.LeslieOBGYN, MikeNYC_runner and 29 others
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LindaRN_retired
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Jul 22, 2024 at 8:29 PM#9

One thing that is still open after MounjBrad’s answer:

Whether anyone has held at a sub-maximal dose long term and kept the result, or whether the maintenance data only exists at 2.4mg?

33 11LondonLisa, mike_nyc, VendorMark and 30 others
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emily_PDX
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Jul 23, 2024 at 12:12 AM#10

Reporting back.

Update — tachyphylaxis to the gastric effect, persistence of the appetite effect. Two curves, and I had been watching the wrong one.

39 14PeptideSynthNJ, Dr.KarenChen, Dr.NateNeph and 36 others
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