philipkglass
14 hours ago
This is subscriber-walled, but the full article is available here:
https://web.archive.org/web/20240909093450/https://www.statn...
The key reason Pfizer passed was that executives didn't think patients would accept a new therapy that required injection to administer:
Despite our emerging results, the Pfizer executives in charge of research and external alliances told us the company did not want to develop a new diabetes therapy that required injection, a space held exclusively by insulin since 1922. They gave us a year to find a way to deliver GLP-1 via transnasal, transcutaneous, or oral administration. Effective delivery by any of these approaches would have been great, but we knew success was unlikely in the year they gave us. Our effort was predictably unsuccessful, and after four years, Pfizer terminated our agreement as permitted under the alliance contract.
The first commercial GLP-1 receptor agonist, Exenatide, went to market as an injectable medication in 2005 [1]. Orally delivered GLP-1 medications didn't come to market until 2019 when orally dosed semaglutide was approved as Rybelsus [2].
Now that injected GLP-1 drugs are among the most-prescribed drugs in America, I wonder if drug company executives are going to be more receptive to drug candidates that require injections. There are a lot of molecules (especially peptides) that are degraded by the digestive system; maybe people will be more willing to inject medications when so many have started self-injecting for GLP-1 drugs or know someone who has.
Scaevolus
14 hours ago
Self-injecting feels like a scary, painful, dangerous procedure and becomes completely boring by the third repetition.
firesteelrain
13 hours ago
The proprietary injector mechanism like for Mounjaro makes it really easy for users. Even compounded versions of it use tiny insulin needles that have near zero pain when injected into the subcutaneous portion of like the stomach while pinched.
Source: I took compounded Mounjaro and compounded Ozempic/semaglutide.
OptionOfT
12 hours ago
Do you still take it? I'm looking for some more information on compounded GLP-1 and their safety.
firesteelrain
11 hours ago
I stopped taking compound Mounjaro a year ago. I started semaglutide in Sept and stopped because it made me sick (throwing up, other non desirable GI effects). My body couldn’t handle semaglutide.
sincerely
2 hours ago
Reportedly retatruide doesn’t cause nausea in as many people, but can still cause diarrhea. May still be worth looking into if you’re interested
Projectiboga
8 hours ago
Type 1 insulin user. One the alcohol should dry before the needle goes in. Two faster is better, within reason. Three about one in a few hundred shots hits a nerve bundle. That really hurts, but resolves after a short while. Both insulin and these GLP-1 injections are subcutaneous not intravenous which once a patient gets the skill it becomes like riding a bike, in that it becomes easier than imagined.
stavros
13 hours ago
It really helps that the needles are hair-thin and short.
DANmode
12 hours ago
Are you using this?
cm2187
13 hours ago
I concur, exactly the way I felt before and after.
amelius
13 hours ago
Isn't there some long term harm to the skin if you do this often?
sowbug
10 hours ago
Insulin users would have better answers to this question, since they might inject multiple times a day, whereas GLP-1 users typically inject only weekly.
But in either case, the answer for subcutaneous injections using needles sized 29g and smaller is no.
cperciva
9 hours ago
Injection drug user here. We're advised to rotate injection sites but the largest issue is actually the insulin (most of it diffuses into the bloodstream but there is a local effect, usually taking the form of increased fat accumulation at sites of repeated injection), not the "making holes in the skin" part.
I don't know the pharmacokinetics of GLP-1 drugs but my guess is that they don't have the same sort of effects on SC tissue?
Before I had a CGM I did somewhere around 20,000 blood glucose tests over the course of a decade using about 1 cm^2 of forearm and the skin there is clearly not in great shape -- but it's worsened on the level of "looks like the skin of someone who is a decade older or spent too long in the sun" rather than anything medically problematic.
jaggederest
9 hours ago
> I don't know the pharmacokinetics of GLP-1 drugs but my guess is that they don't have the same sort of effects on SC tissue?
They do, but nothing like insulin does. GLP-1 drugs are more centrally and viscerally active than subcutaneously active, so the effects locally are more related to the physics of injecting solutions subcutaneously than the drugs themselves. They're also much smaller doses than are needed for insulin in general, so the volume averaged over a week is pretty tiny.
Also, as a result of the relative lack of local activity, injection sites are basically unlimited (anywhere from above the knee to above the elbow, except the neck) without fear of lipohypertrophy in the local area.
wombatpm
8 hours ago
No. So long as you rotate your injection site. My son is T1 and before his pump was getting 4-6 injections a day.
nkrisc
12 hours ago
Seems completely negligible to the normal amount of tiny cuts and scrapes you accumulate on any given day.
dgares
11 hours ago
Yes, but only if you do it in the same spot every time.
thaumasiotes
13 hours ago
To the skin? Probably not.
Heroin addicts and presumably anyone else who frequently injects into a vein can cause damage to the veins.
nextos
13 hours ago
FWIW, Novo Nordisk also tried to kill their GLP-1 effort several times according to the project lead, Lotte Bjerre Knudsen: https://archive.is/oLnBl
In large organizations, I guess a big chunk of success comes from being able to navigate all these political ups and downs.
RobotToaster
13 hours ago
I wonder how many other great medical innovations have disappeared because of such bureaucracy.
estearum
9 hours ago
Bureaucracy? This is the same type of go/no-go decision that R&D orgs have to make with incomplete information and immense costs every day. But with less complete information (no in-human data → 70-90% failure rate) and more immense costs (a couple hundred million dollars to get it through trials).
The problem is the cost and risk profile of drug development. With those parameters where they are, there will be countless "bureaucratic errors" of foregone opportunities, most of which we'll never even learn about.
lotsofpulp
7 hours ago
Technically, they disappeared because of limited resources. If every pharmaceutical organization had unlimited funding to run unlimited trials, then they would.
DANmode
12 hours ago
How long do you have?
https://www.sciencenews.org/article/vaccine-beer-polyomaviru...
petesergeant
12 hours ago
It's worth bearing in mind that the reality of self-injector pens with tiny needles today is not the reality of syringes 30 years ago.