This isn't just an oral formulation of tirzepatide, right? The article sort of hints at this but doesn't really come out and say it one way or the other.
> Eli Lilly’s pill works in a similar way to Wegovy, Ozempic, and Novo Nordisk’s diabetes pill Rybelsus, targeting a gut hormone called GLP-1 to suppress a person’s appetite and regulate blood sugar.
(These three are all just different names for Semaglutide.)
> But unlike those three medications, Eli Lilly’s pill is not a peptide medication.
> ...
> But so-called small molecule pills [orforglipron] will at least be easier for Eli Lilly to manufacture than injections.
No, it's not a reformulation of tirzepatide. Orforglipron is a small molecule with a molecular mass of 883 g/mol and tirzepatide is a large molecule peptide six tims larger, with a molecular mass of 4813 g/mol.
The Wikipedia pages are decent -- the picture makes it fairly obvious how much smaller orforglipron is than tirzepatide even if you don't know how to read chemical structures; just count atoms!
It does say it in those two later sentences you quoted:
But unlike those three medications, Eli Lilly’s pill is not a peptide medication.
But so-called small molecule pills [orforglipron] will at least be easier for Eli Lilly to manufacture than injections.
In medicinal chemistry parlance, a "small molecule drug" normally means one that can be synthesized by flasks-and-beakers organic chemistry of the sort one learns in an organic synthesis class. (And it has a lower molecular weight than peptide or biologic drugs, hence the name.) Peptide drugs are synthesized by a specialized kind of organic chemistry that mimics aspects of protein synthesis:
The industrially relevant thing is that small molecule drugs typically cost less to produce, once the molecule goes into full scale production. Lower cost is an advantage for the first manufacturer while the drug is under patent and it's an advantage for buyers once the drug's patent exclusivity expires.
It could be the biggest drug. It might get out of phase 3. It may get approval very soon. And of course, "may be a game changer."
When the news is this fast and loose with anything that even looks like a fact how am I not to see this as rank manipulation? There is nothing critical in this article except for how hard doctors and insurance companies might be pressed to prescribe it.
Then they end with this gem:
"But Seigerman said it will also put pressure on smaller companies developing pills, such as Structure Therapeutics, to find a partner that can help them compete in the weight loss drug market with pharmaceutical behemoths like Eli Lilly. "
Oh. I see. It's not just manipulation but dumb protectionist gate keeping.
I don't understand what your criticism is here exactly. Of course Eli Lilly will release a press release if the results of a clinical trial are good but that doesn't make the underlying research (published in the Lancet [1]) suspect in any way. Clinical trials are overseen by the FDA and frequently conducted by third party research scientists without a financial stake in the long term success of the intervention being studied. In this case, it appears that the study authors were researchers at Velocity Clinical Research and they found significant body weight loss with side effects comparable with other GLP-1 agonists. Skepticism might be warranted, particularly until phase 3 trials are conducted, but mindless cynicism hardly seems warranted.
Those wondering about the mouthful of a name that is "orforglipron" may be interested in the INN (international nonproprietary name) standard for generic drugs. That name is a "generic" or "nonproprietary" name.
Those typically have a "stem" which indicate the mechanism by which the drug works. In this case, it's "-glipron", which you can parse as "glipr" -- GLP-1 receptor -- and "on" -- it's an "agonist", or something that turns "on" the receptor. So "-glipron"s are drugs which agonize, or activate, the GLP-1 receptor. There are other gliprons in trials, including danuglipron (https://en.wikipedia.org/wiki/Danuglipron) from Pfizer, and many others that don't have assigned INNs.
Semaglutide and liraglutide also agonize GLP-1, so why aren't they gliprons? Because chemically they are analogs of the naturally occurring GLP-1 peptide, so they get the -glutide (GLUcagon-like pepTIDE) stem.
The pipeline for weight loss drugs is quite full and can be found here...
>Industry data provider IQVIA pulled together a list of the current obesity pipeline, which features 124 medicines altogether: 61 in phase 1, 47 in phase 2, eight in phase 3 and eight on the market.
No medication to make people ripped (yet). Though I have to imagine someone is trying to find a way to induce myostatin-related muscle hypertrophy without gene therapy.
I see this pathway, GLP-1 successors, and rewriting adipose tissue memory [4] [5] as the holy grail of weight loss, muscle gain, and weight/composition management with little effort. Diet and exercise? Old and busted. Hormone orchestration is the new hotness (with perhaps a touch of gene therapy if needed). "We fixed the glitch."
the bodybuilding scene has gotten more advanced than just steriods, for example:
- SARMs (selective androgen receptor modulators) - eg ostarine - they hit your muscles androgen receptors selectively, nominally other receptors (ie reproductive) are skipped over
- SERMS (selective estrogen receptor modulators) - typically used to reduce gynecomastia after steroid use, but interestingly one, clomiphene or enclomiphene, blocks estrogen reception in the pituitary, making it think hormone production is too low - so tells your body to manufacture more testosterone (yes, estrogen receptor blockage yields testosterone production).. this is the closest we have to a fertility drug and is prescribed as a fertility drug in women
- cardarine - PPAR delta activator, activates metabolic pathways and used by athletes for doping - quite an interesting drug because it normalizes one's metabolism, increases athletic performance, lowers cholesterol, etc, wow! though to activate a particular minor cancer pathway.. never tested in humans since it gave animal models turbocancer. used by many athletes
But yea, most of these are going to blanket increase risks for various things - strokes, clot, heart attack... messing about with hormones can be quite damaging albeit I would take a SARM or a SERM before taking straight hormones. Cardarine is quite scary because of the cancer concern
SARMs are just relatively ineffective anabolic steroids. They likely have the same health drawbacks, through the same mechanisms, in addition to the drawbacks of being understudied and less effective.
SERMs aren't muscle-building.
Don't take SARMs or other AAS (aside from TRT under the supervision of a physician) unless you want to die young.
Get the nation a steady diet of HFCS's and related "sugar substitutes". Check. Foster drug science to create ways to get people thin, again. Check.
Gets you coming and going. Noice.
32 comments
[ 2.7 ms ] story [ 86.8 ms ] thread> Eli Lilly’s pill works in a similar way to Wegovy, Ozempic, and Novo Nordisk’s diabetes pill Rybelsus, targeting a gut hormone called GLP-1 to suppress a person’s appetite and regulate blood sugar.
(These three are all just different names for Semaglutide.)
> But unlike those three medications, Eli Lilly’s pill is not a peptide medication.
> ...
> But so-called small molecule pills [orforglipron] will at least be easier for Eli Lilly to manufacture than injections.
The Wikipedia pages are decent -- the picture makes it fairly obvious how much smaller orforglipron is than tirzepatide even if you don't know how to read chemical structures; just count atoms!
https://en.wikipedia.org/wiki/Orforglipron
https://en.wikipedia.org/wiki/Tirzepatide
> tirzepatide is a large molecule peptide
No, the molecule (per wikipedia) is significantly smaller.
But unlike those three medications, Eli Lilly’s pill is not a peptide medication.
But so-called small molecule pills [orforglipron] will at least be easier for Eli Lilly to manufacture than injections.
In medicinal chemistry parlance, a "small molecule drug" normally means one that can be synthesized by flasks-and-beakers organic chemistry of the sort one learns in an organic synthesis class. (And it has a lower molecular weight than peptide or biologic drugs, hence the name.) Peptide drugs are synthesized by a specialized kind of organic chemistry that mimics aspects of protein synthesis:
https://en.wikipedia.org/wiki/Peptide_synthesis
The industrially relevant thing is that small molecule drugs typically cost less to produce, once the molecule goes into full scale production. Lower cost is an advantage for the first manufacturer while the drug is under patent and it's an advantage for buyers once the drug's patent exclusivity expires.
If Deflate had not been picked as compression algorithm name, it surely would be a fine name for a weight loss drug.
When the news is this fast and loose with anything that even looks like a fact how am I not to see this as rank manipulation? There is nothing critical in this article except for how hard doctors and insurance companies might be pressed to prescribe it.
Then they end with this gem:
"But Seigerman said it will also put pressure on smaller companies developing pills, such as Structure Therapeutics, to find a partner that can help them compete in the weight loss drug market with pharmaceutical behemoths like Eli Lilly. "
Oh. I see. It's not just manipulation but dumb protectionist gate keeping.
Depressing.
That's pretty substantial. Obviously no one knows what Phase 3 will show, but cynicism seems unwarranted at this point.
https://investor.lilly.com/news-releases/news-release-detail...
[1] https://www.thelancet.com/journals/lancet/article/PIIS0140-6...
Those typically have a "stem" which indicate the mechanism by which the drug works. In this case, it's "-glipron", which you can parse as "glipr" -- GLP-1 receptor -- and "on" -- it's an "agonist", or something that turns "on" the receptor. So "-glipron"s are drugs which agonize, or activate, the GLP-1 receptor. There are other gliprons in trials, including danuglipron (https://en.wikipedia.org/wiki/Danuglipron) from Pfizer, and many others that don't have assigned INNs.
Semaglutide and liraglutide also agonize GLP-1, so why aren't they gliprons? Because chemically they are analogs of the naturally occurring GLP-1 peptide, so they get the -glutide (GLUcagon-like pepTIDE) stem.
I don't know why tirzepatide got that name. It's a peptide, so "-tide" makes sense, but it's actually listed as a "various" exception in the master document of INNs: https://iris.who.int/bitstream/handle/10665/379226/978924009....
>Industry data provider IQVIA pulled together a list of the current obesity pipeline, which features 124 medicines altogether: 61 in phase 1, 47 in phase 2, eight in phase 3 and eight on the market.
https://www.fiercebiotech.com/biotech/late-breaking-obesity-...
Same as people who can't be bothered to comb their hair.
which was definitely considered a desirable look at various times.
I see this pathway, GLP-1 successors, and rewriting adipose tissue memory [4] [5] as the holy grail of weight loss, muscle gain, and weight/composition management with little effort. Diet and exercise? Old and busted. Hormone orchestration is the new hotness (with perhaps a touch of gene therapy if needed). "We fixed the glitch."
[1] https://en.wikipedia.org/wiki/Myostatin
[2] https://www.jci.org/articles/view/148372
[3] https://today.uconn.edu/2025/02/next-generation-of-weight-lo...
[4] https://portlandpress.com/bioscirep/article/33/5/e00065/5610...
[5] https://www.nature.com/articles/s41586-024-08165-7
(not a medical professional, but i do not recommend anabolic steroid use except under the recommendation and supervision of a medical professional)
> (not a medical professional, but i do not recommend anabolic steroid use except under the recommendation and supervision of a medical professional)
That goes double for any kind of myostatin inhibitor, of course.
But yea, most of these are going to blanket increase risks for various things - strokes, clot, heart attack... messing about with hormones can be quite damaging albeit I would take a SARM or a SERM before taking straight hormones. Cardarine is quite scary because of the cancer concern
SERMs aren't muscle-building.
Don't take SARMs or other AAS (aside from TRT under the supervision of a physician) unless you want to die young.