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ForumsOral GLP-1 AgonistsOral semaglutide bioavailability optimization — need advice

Oral semaglutide bioavailability optimization — need advice

mike_nyc Thu, Mar 19, 2026 at 9:57 AM 7 replies 670 viewsPage 1 of 2
mike_nyc
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Mar 19, 2026 at 9:57 AM#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.

What I actually want to know is how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly.

Tell me what I have not thought of.

40 10maya_sedona, stefan_berlin, Dr.EM_Chicago and 37 others
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Dr.GutHealth
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Mar 19, 2026 at 10:06 AM#2

Taking the question as asked, rather than the general version of it. 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.

Last edited: Mar 19, 2026 at 3:06 PM
39 9tyler_CSCS, VanRx_Mike, steve_okc and 36 others
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SurmountFan_IN
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Mar 19, 2026 at 10:15 AM#3
Dr.GutHealth 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 Dr.GutHealth, and the qualification matters more than the agreement. Worth adding that the tablet is taken daily, so a missed dose costs far less than a missed weekly injection. That is a genuine advantage nobody lists.

38 8traveltech_sara, AttorneyGrant, DebRD_ATL and 35 others
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MikeNYC_runner
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Mar 19, 2026 at 10:24 AM#4
mike_nyc 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.

Can confirm the pattern mike_nyc describes. 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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sophie_paris
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Mar 19, 2026 at 11:13 AM#5

From the other side of the consultation, briefly. Whatever the answer turns out to be, the method for getting there is the same: state the assumption, do the arithmetic in public, and invite the correction. That is slower than asserting, and it is the only version that survives being wrong.

Last edited: Mar 19, 2026 at 4:13 PM
36 6BethLabQueen, ChrisMacros, KetoKyle and 33 others
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