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ForumsOral GLP-1 AgonistsOral sema absorption enhancer SNAC — anyone have experience?

Oral sema absorption enhancer SNAC — anyone have experience?

dave_SLC Thu, Apr 4, 2024 at 11:27 PM 55 replies 2,928 viewsPage 1 of 11
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dave_SLC
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Apr 4, 2024 at 11:27 PM#1

I switched from injectable to oral semaglutide for travel reasons and the fasting window is proving harder to hold than the injection ever was.

So the question, as narrowly as I can put it: how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly.

Numbers rather than impressions, if you have them.

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JessicaH_TX
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Apr 5, 2024 at 1:37 AM#2

This one has a reasonably settled answer, so here it is. The OASIS programme put 50mg oral in the same territory as 2.4mg injectable — around 15% mean weight loss — but it needed a dose 20 times larger to get there because almost none of the tablet is absorbed. The dose numbers are not comparable across routes and quoting them side by side confuses people.

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mike_mod
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Apr 5, 2024 at 3:47 AM#3
JessicaH_TX said:
The OASIS programme put 50mg oral in the same territory as 2.4mg injectable — around 15% mean weight loss — but it needed a dose 20 times larger to…

That is correct as far as it goes, and here is where it stops going. The absorption variability is real, but it partly averages out over weeks — the steady-state trough is less erratic than any single day would suggest. Where it bites is in the first fortnight, when people conclude the tablet does nothing.

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Dr.PulmRoch
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Apr 5, 2024 at 5:57 AM#4
dave_SLC said:
I switched from injectable to oral semaglutide for travel reasons and the fasting window is proving harder to hold than the injection ever was.

Same position here, arrived at the long way round. Oral semaglutide is absorbed in the stomach with the help of SNAC, which locally raises pH and protects the peptide long enough to cross. That mechanism is fragile: bioavailability is roughly 1% and highly sensitive to gastric contents, so a mouthful of coffee genuinely changes the exposure. This is why the label wants 30 minutes and no more than half a glass of plain water.

Last edited: Apr 5, 2024 at 6:57 AM
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KevinCompounds
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Apr 5, 2024 at 6:48 PM#5

Clinical perspective, offered as context rather than as advice. The version of this that has an answer is narrower than the version being asked. Narrow it and it becomes tractable; leave it broad and the thread will produce nine confident and incompatible replies.

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