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ForumsOral GLP-1 AgonistsSmall molecule vs peptide GLP-1 agonists — need advice

Small molecule vs peptide GLP-1 agonists — need advice

GraceAZ_72 Sat, Dec 28, 2024 at 11:36 PM 8 replies 1,709 viewsPage 1 of 2
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GraceAZ_72
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Dec 28, 2024 at 11:36 PM#1

On 25mg oral, four months in, and my results are closer to the low-dose injectable arm than to the numbers being quoted for 50mg.

The practical numbers: about 1% oral bioavailability, 30 minutes fasted before food, no more than 120ml of plain water, and coffee counts as food for this purpose.

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.

If the honest answer is that nobody knows, that is a useful answer and I would rather have it.

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LipidDoc_ATL
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Dec 28, 2024 at 11:57 PM#2

Answering the narrow version, because the broad one does not have a single answer. 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.

Correct me if the detail matters more than I have assumed.

Last edited: Dec 29, 2024 at 4:57 AM
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FitDadDave
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Dec 29, 2024 at 12:18 AM#3
LipidDoc_ATL 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…

Agreeing with LipidDoc_ATL, and the qualification matters more than the agreement. 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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kim_atl_prep
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Dec 29, 2024 at 12:38 AM#4
GraceAZ_72 said:
On 25mg oral, four months in, and my results are closer to the low-dose injectable arm than to the numbers being quoted for 50mg.

This matches mine closely enough to be worth saying so. 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.

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Dr.NutriCornell
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Dec 29, 2024 at 2:28 AM#5

From the other side of the consultation, briefly. The distinction that resolves most of these threads is between what is true on average and what is true for one person. Both are real; they answer different questions and get quoted as if they were the same one.

Last edited: Dec 29, 2024 at 4:28 AM
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