[CGMthrowaway]

Sublingual is even harder. The sublingual mucosa is thin but selective. It strongly favors molecules that are small, lipophilic and uncharged. Semaglutide is about 8-10x too big, highly polar and charged.

Injection is really the only method with any substantial bioavailability. BUT, low (<1%) bioavailability does not necessarily mean useless.

[cassepipe]

> BUT, low (<1%) bioavailability does not necessarily mean useless.

Can you say more about that point ?

[nerdsniper]

If the drug has a relatively low marginal cost of production, and the stomach just breaks down 99% of it without side effects, you can just manufacture 100x more, give it orally, and eat the cost of the 99% that gets lost along the way.

Injectable Semaglutide/Tirzepatide (>99.8% pure) are currently sold at a profit from China for around $2-3/weekly dose. Rybelsus (oral semaglutide) is sold at roughly the same cost per milligram, even though it's made in FDA-approved facilities (you just need to take >= 40x more milligrams per month, bringing it to $1000/month in the USA)

So manufacturing oral doses 100x higher than injectable seems to be economically viable.