3 ms·

Yep, I think it is. The point is there's almost no history of oral peptides, other than stomachs destroying them. FTA: "So to summarize the state of the art in

Yep, I think it is. The point is there's almost no history of oral peptides, other than stomachs destroying them. FTA: "So to summarize the state of the art in oral peptide delivery: there are exactly two FDA-approved products that use permeation enhancers to get peptides into your bloodstream through your GI tract. Both achieve sub-1% bioavailability. Both required over a decade of development, thousands of clinical trial participants, and hundreds of millions of dollars."

pstuart 8mo ago
Would a sublingual dose be possible/more effective? Research in other (um, yeah, medicinal!) compounds shows that it can be an effective pathway to the bloodstream rather than trying to survive the digestive system.
- rodarmor 8mo ago
  It would be hilarious if people wound up snorting or boofing their GLP-1s (≧▽≦)
  - deleted 8mo ago
    [deleted]
  - pstuart 8mo ago
    Insufflation for medicinal purposes if it works and doesn't cause harm seem like a win. Less needles == more use.
    - LoganDark 8mo ago
      Ancedotal but it's really hard for me to do insufflation because of the discomfort. Of course if my life depended on it I could probably do it but otherwise I'd rather not.
- CGMthrowaway 8mo ago
  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 8mo ago
    > BUT, low (<1%) bioavailability does not necessarily mean useless. Can you say more about that point ?
    - nerdsniper 8mo ago
      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.

pstuart 8mo ago

Would a sublingual dose be possible/more effective? Research in other (um, yeah, medicinal!) compounds shows that it can be an effective pathway to the bloodstream rather than trying to survive the digestive system.

rodarmor 8mo ago
It would be hilarious if people wound up snorting or boofing their GLP-1s (≧▽≦)
- deleted 8mo ago
  [deleted]
- pstuart 8mo ago
  Insufflation for medicinal purposes if it works and doesn't cause harm seem like a win. Less needles == more use.
  - LoganDark 8mo ago
    Ancedotal but it's really hard for me to do insufflation because of the discomfort. Of course if my life depended on it I could probably do it but otherwise I'd rather not.
CGMthrowaway 8mo ago
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 8mo ago
  > BUT, low (<1%) bioavailability does not necessarily mean useless. Can you say more about that point ?
  - nerdsniper 8mo ago
    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.