Eli Lilly will soon release key data on its weight loss pill orforglipron | Hacker News Reader

Eli Lilly will soon release key data on its weight loss pill orforglipron

cnbc.com

32 pointstoomuchtodo29 comments

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.

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....

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.

https://www.fiercebiotech.com/biotech/late-breaking-obesity-...

https://investor.lilly.com/static-files/cdedba2e-c4a7-4047-9... (pages 40-41)

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!

https://en.wikipedia.org/wiki/Orforglipron

https://en.wikipedia.org/wiki/Tirzepatide

Also, tirzepatide is a peptide whereas orforglipron is not.

GP mentioned that.

> tirzepatide is a large molecule peptide

> This isn't just an oral formulation of tirzepatide, right?

No, the molecule (per wikipedia) is significantly smaller.

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:

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.

Perhaps I should have been explicit that I meant "say it explicitly," though I thought it was pretty clear.

In a world were everyone is lean and ripped, i wonder if it being overweight will become the new sexy again

No, it'll mean 'Im too lazy to go to my GP and get weight loss medication'.

Same as people who can't be bothered to comb their hair.

> Same as people who can't be bothered to comb their hair.

which was definitely considered a desirable look at various times.

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.

There is a pathway to target that encourages muscle growth without exercise, but it increases cancer risk.

Uh, also heart attack / stroke. (We're talking about anabolic steroids, right?)

Myostatin inhibitor mechanisms [1] [2] [3].

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)

Yeah, I'm less optimistic we'll crack the pharma muscle gain without huge negative side effects any time soon, but it would be nice.

> (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.

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.

P/E of 73. What can go wrong?

Fun fact, Orforglipron got named when the lead scientist's cat sat on their keyboard. /s

Yes, the name does seem like they're just fucking with us.

Sounds like "Oral formulation GLP-1", which is what it is? That won't be the brand name.

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.

It's a horrible name. I guess we already discovered so many compounds that nice-sounding names are exhausted.

If Deflate had not been picked as compression algorithm name, it surely would be a fine name for a weight loss drug.

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.

Depressing.

Phase 2 clinical trials showed 14.7% mean weight reduction at 36 weeks in adults.

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...

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