12/27/2025 at 10:07:20 PM
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.
by philipkglass
12/27/2025 at 11:17:51 PM
FWIW, Novo Nordisk also tried to kill their GLP-1 effort several times according to the project lead, Lotte Bjerre Knudsen: https://archive.is/oLnBlIn large organizations, I guess a big chunk of success comes from being able to navigate all these political ups and downs.
by nextos
12/27/2025 at 11:37:29 PM
I wonder how many other great medical innovations have disappeared because of such bureaucracy.by RobotToaster
12/28/2025 at 3:24:16 AM
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.
by estearum
12/28/2025 at 5:55:44 AM
Technically, they disappeared because of limited resources. If every pharmaceutical organization had unlimited funding to run unlimited trials, then they would.by lotsofpulp
12/28/2025 at 12:32:29 AM
How long do you have?https://www.sciencenews.org/article/vaccine-beer-polyomaviru...
by DANmode
12/27/2025 at 10:19:40 PM
Self-injecting feels like a scary, painful, dangerous procedure and becomes completely boring by the third repetition.by Scaevolus
12/27/2025 at 11:15:01 PM
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.
by firesteelrain
12/28/2025 at 12:46:50 PM
Similarly, I grabbed one of the over-the-counter CGM biosensors (Stelo) to gather some data for a couple of weeks and the initial fear of "holy hell, I'm slamming a needle into my arm with something stuck to it" goes away as soon as you slap the injector release.Just one little clap sound, you feel a little pat on your arm, and the sensor's already made it where it needed to with no pain.
When you remove the sensor it's a little bit of a shock when you see the sensor wire and realize just how small it was and how you never felt it run around inside your arm for a couple weeks.
by kotaKat
12/28/2025 at 5:06:33 PM
fyi: the impact is an intentional decision. if your nerve endings are signaling something else(hot, cold, movement, etc), a needle prick can get blurred with the rest or ignored altogether. I suspect the bang/clag CGM applicators produce are much the same.and, for me, its always been the needle moving around thats been mentally disturbing. digging around vecause they missed for the blood draw, trying to hold a large vaccination dose steady as it needs to be injected over 20seconds. So, I suspect the speed itself reduces discomfort.
by butvacuum
12/28/2025 at 12:37:26 AM
Do you still take it? I'm looking for some more information on compounded GLP-1 and their safety.by OptionOfT
12/28/2025 at 1:14:10 AM
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.by firesteelrain
12/28/2025 at 10:08:04 AM
Reportedly retatruide doesn’t cause nausea in as many people, but can still cause diarrhea. May still be worth looking into if you’re interestedby sincerely
12/28/2025 at 4:13:04 AM
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.by Projectiboga
12/27/2025 at 11:07:16 PM
It really helps that the needles are hair-thin and short.by stavros
12/28/2025 at 12:32:56 AM
Are you using this?by DANmode
12/28/2025 at 12:34:06 AM
Yes.by stavros
12/28/2025 at 5:50:41 AM
For a brief moment I thought you were Stavros Halkias.by tresdots
12/28/2025 at 10:31:03 AM
The only man to successfully battle and defeat glp-1's in war. his getting fit series is genuinely motivational. But not for any of the right reasons, lol.by mptest
12/27/2025 at 11:15:40 PM
I concur, exactly the way I felt before and after.by cm2187
12/27/2025 at 11:44:34 PM
Isn't there some long term harm to the skin if you do this often?by amelius
12/28/2025 at 3:00:07 AM
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.
by sowbug
12/28/2025 at 3:31:17 AM
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.
by cperciva
12/28/2025 at 4:01:36 AM
> 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.
by jaggederest
12/28/2025 at 6:08:15 PM
I’ve been diabetic for 30 years, and for more than twenty of those I did multiple daily measurements by pricking my fingertips and multiple insulin injections per day. Now I wear a sensor that I replace every two weeks and a catheter (which I change about once a week).I really don’t understand this phobia of needles at all. After two days with one system or the other, you get used to it—there’s no pain, it’s just a mental issue of “having to make the gesture.”
My friends used to laugh at how normal it was for me to inject insulin outside a restaurant, while walking, chatting, and smoking at the same time.
by UomoNeroNero
12/28/2025 at 4:38:04 AM
No. So long as you rotate your injection site. My son is T1 and before his pump was getting 4-6 injections a day.by wombatpm
12/27/2025 at 11:49:48 PM
To the skin? Probably not.Heroin addicts and presumably anyone else who frequently injects into a vein can cause damage to the veins.
by thaumasiotes
12/28/2025 at 1:44:13 AM
Yes, but only if you do it in the same spot every time.by dgares
12/28/2025 at 12:19:04 AM
Seems completely negligible to the normal amount of tiny cuts and scrapes you accumulate on any given day.by nkrisc
12/27/2025 at 10:42:11 PM
[dead]by s5300
12/28/2025 at 12:51:09 AM
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.by petesergeant
12/28/2025 at 7:21:25 PM
Pfizer has been resting on their laurels ever since it struck gold with boner pills and Lipitor. Viagra made it rain beaucoup bucks and rewired the entire firm to prioritize commercial sales and marketing over real scientific clinical development. Pfizer is optimized for sales over research and development. Now they primarily acquire and license a bunch of me-too drugs and late-stage acquisitions vs creating their own homegrown breakthroughs.Pfizer's strengths are regulatory compliance, M&A and global manufacturing. They suck at research and clinical development. Losing the GLP-1 race was predictable as they simply don't prioritize emerging science compared to other mid-sized and large pharmas.
by randycupertino