A brief history of oral peptides(seangeiger.substack.com)
58 points by odedfalik 1 day ago | 7 comments
bonsai_spool 0 minutes ago
I'm not a specialist but I think there are some stapled peptides that do show appreciable uptake, so this is not a complete history.

Nielsen DS et al. 2017. Orally Absorbed Cyclic Peptides. Chemical Reviews.

https://sci-hub.ru/10.1021/acs.chemrev.6b00838

celltalk 3 hours ago
It’s a great read but is this really the history of oral peptides?
abainbridge 2 hours ago
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 56 minutes 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.
CGMthrowaway 51 minutes 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.

rodarmor 53 minutes ago
It would be hilarious if people wound up snorting or boofing their GLP-1s (≧▽≦)
maxbond 2 minutes ago
I can't imagine a doctor ever advising you to snort anything, but people take suppositories all the time. If it was more bioavailable and that allowed for a much lower price, I'm sure some people who's insurance wouldn't cover the medication would do it. People who've been struggling with a chronic illness like obesity for a long time will usually do pretty much anything if it works.
Kaminsk13 1 day ago
I'm not sure why the hims investors ever thought that this was legal
InsideOutSanta 3 hours ago
They probably didn't, they just took the bet that this was one of the crimes that are currently legal, like crypto scams, environmental crimes, bribery, and tay evasion for the rich.
badrequest 2 hours ago
Some of the most profitable ventures this century have been objectively illegal, but when you know you won't go to prison for violating the law, why would you care to follow it?
pixl97 51 minutes ago
The process of chlorinating water was first done illegally.
CGMthrowaway 44 minutes ago
Also:

  human dissection (grave robbing)
  translating the Bible into English
  silk production outside of China (death penalty for exporting worm eggs)
  rubber production in Asia (seeds smuggled out of Brazil)
  the Underground Railroad
  heliocentrism
  AIDS treatment (see Dallas Buyers Club)
  Needle exchange programs for IV drug users
  Ridesharing/airbnb/napster (obvious ones)
  SF gay marriage licenses (in defiance of CA law)
maxbond 32 minutes ago
> The process of chlorinating water was first done illegally.

I tried to find a source on this but it doesn't seem to be true? The first chapter of this book describes the history of chlorination: https://upload.wikimedia.org/wikipedia/commons/f/fd/Chlorina... (which is a source Wikipedia cites) and it doesn't appear to mention anything about illegally chlorinating water. After looking in that book I asked ChatGPT to find a source for the claim, and it reported the claim was false. Chlorination was initially controversial but I can't find anything claiming it was illegal?

kps 3 hours ago
The charitable assumption is that investors weren't aware it was a problem.
Boot2Root 1 day ago
Appreciate the perspective on the risk of dubious formulations. Consequences are far more than cosmetic.
badc0ffee 1 hour ago
Informative article but I feel like it could have benefited from a paragraph about what Hims is. I had never heard of them before.
ftchd 3 hours ago
thanks, needed this for a mogging session later
ydai0531 1 day ago
great read!