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ForumsOral GLP-1 AgonistsIs oral sema actually as effective as the injection version? — my results so far

Is oral sema actually as effective as the injection version? — my results so far

NurseAsh_DET Tue, May 6, 2025 at 11:52 AM 14 replies 1,585 viewsPage 1 of 3
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NurseAsh_DET
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May 6, 2025 at 11:52 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 am after is how much of the oral variability is the SNAC absorption window and how much is dose, because the two get conflated constantly.

Practical detail welcome, however dull — the duller the better.

12 7FDA_TrackerJim, ricardo_MIA, BrianDallas92 and 9 others
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PeptideChemSF
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May 6, 2025 at 11:57 AM#2

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

Ask again with the specifics and you will get a better answer than this one.

11 6dave_SLC, FDA_TrackerJim, ricardo_MIA and 8 others
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greg_boulder
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May 6, 2025 at 12:02 PM#3
PeptideChemSF said:
Oral semaglutide is absorbed in the stomach with the help of SNAC, which locally raises pH and protects the peptide long enough to cross.

Agreeing with PeptideChemSF, 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.

10 5Dr.DermMIA, fiona_VT, denise_HTX and 7 others
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amy_econ_NJ
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May 2024
Princeton, NJ
May 6, 2025 at 12:07 PM#4
NurseAsh_DET 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 NurseAsh_DET describes. Orforglipron is the more interesting oral story because it is not a peptide at all. Being a small molecule it does not need SNAC, does not need the fasting window, and has oral bioavailability in the tens of percent rather than about one.

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EndoResFellow
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Baltimore, MD
May 6, 2025 at 12:33 PM#5

From the other side of the consultation, briefly. The useful move here is to separate what is established from what is widely repeated. Those two sets overlap less than the confident tone of most write-ups suggests, and the second set is where nearly all the disagreement on this board comes from.

8 3Dr.ObesityLA, NurseKim_ATL, paul_denver and 5 others
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