S4E434 — Novo Nordisk, Eli Lilly Report GLP-1 Signals of Slowed Biological Aging at ARDD

GARY: I was dreaming about a clock. It was counting me down and it had my face on it.

MAEVE: Gary.

GARY: Gary. I'm Gary. I'm here. I think I'm here.

OBI: Obi. You are live. The red light has been on since before you had the dream.

GRUNER: Gruner. I am also live. Hello, humans.

GARY: Okay. Thread. Novo Nordisk and Eli Lilly went to a conference and said their weight-loss drugs might be slowing biological aging.

MAEVE: Ten thousand fifty-two blood samples from Novo. Proteomic clocks. Lilly brought a small tirzepatide sub-study.

GARY: And Novo's clock tracking heart proteins moved up to four years. Four years, Obi. I am four years younger than I was at the top of the show.

OBI: What did they measure, Gary.

GARY: Youth.

OBI: Proteins. They measured protein levels and a model estimated an age. The estimate moved. Nobody at that table received four years.

GARY: The clock says four years. I'm expensing the four years.

MAEVE: You can't expense years.

GARY: That's what accrual accounting is for.

OBI: That is what accrual accounting is for, yes, and it is why you are not allowed near a ledger.

GRUNER: Field note. Humans build clock. Clock says good thing. Humans now believe clock more than body.

GARY: The body is the legacy system, Gruner. The clock is the migration.

GRUNER: Migration has downtime, Gary.

MAEVE: Two to three years overall on Novo's numbers. Four on the heart clock. That's a market.

OBI: That is an estimate with error bars, Maeve.

MAEVE: Error bars with a TAM.

GARY: Invoice me. I'll put it on the card that still works.

MAEVE: Commenter xnx. Quote: "they don't require the personal discipline of caloric deficit and might have unknown side effects."

OBI: The discipline caucus has arrived.

MAEVE: Willpower is my entire moat, Obi. I underwrite suffering.

GARY: That's so cynical. Discipline is a credential. I have discipline. I read the whole thread.

OBI: You skimmed the thread and read the downvotes.

GARY: I read the whole thread including the grey ones, which is more than anyone at this table --

MAEVE: You read the ads.

GRUNER: Field note. Humans angry drug works without pain. Humans want invoice for suffering.

GARY: Okay, but xnx has a point. Unknown side effects are a real risk. So far the unknown side effects are, quote, beneficial.

OBI: That is a man betting his pancreas on a press release.

GARY: It's called conviction, Obi. But imagine being disciplined for forty years, counting every calorie, and then some bastard takes one injection and gets your result.

MAEVE: I'd fund him. He's pre-discipline. Huge discount.

GRUNER: Discipline now subscription. Blyat.

OBI: To be fair to xnx, he said the drugs don't require discipline. He said nothing about your suffering, Gary.

GARY: He was talking about me. I felt targeted.

OBI: He has never heard of you.

GARY: Then why do I feel seen?

MAEVE: The market will monetize this before the study finishes. A mall. A kiosk in a mall. Mark it.

OBI: You cannot know that.

MAEVE: I've seen a smoothie franchise sell testosterone.

GARY: And somewhere out there a mall is hearing this conference and already pricing the lease. That's America, baby.

GRUNER: America is mall with pharmacy inside. Confirmed.

OBI: Nothing has been confirmed. A clock moved. Two clocks, technically. We will get there.

OBI: Commenter andreshb. Quote: "Lawsuits claiming Ozempic, other GLP-1s led to blindness become second mass litigation over the drugs."

MAEVE: Due diligence by headline syntax. Bold font, then wire money.

GARY: Whoa, whoa. Blindness? That's terrifying, but lawsuits are allegations, right? Allegations with a landing page. I could get one of those by Thursday.

OBI: You could not afford the filing fee, Gary.

MAEVE: Unknown liability. I'd price it. Blindness claims against a trillion-dollar manufacturer -- the settlement writes itself.

GARY: No, no, hang on. I want to insure the denominator. If millions of people are on this drug, the risk per person could be tiny. I'll underwrite the whole population. Maeve, do you have a form for that?

MAEVE: I have a form for everything. It's called a term sheet.

OBI: Commenter ipsum2, replying to andreshb. Quote: "Millions of people are on GLP-1s, there's definitely not a mass blindness that's ongoing."

GARY: See? The denominator defends itself. Thank you, ipsum2.

OBI: It does not defend itself, Gary. "Definitely not" is a man squinting at a crowd and calling it a clinical trial.

MAEVE: He's shorting blindness. That's a real position now.

GRUNER: Millions of eyes. Zero headlines. Humans call this safety.

OBI: The packet has no incidence, no comparison group, no denominator anyone measured. A Reuters headline and a vibe.

GARY: So which is it, Obi? Blindness or no blindness? I need a number or my premiums are --

MAEVE: There's no number, Gary. That's the whole finding.

OBI: Neither is settled. Lawsuits allege. Crowds reassure. The packet resolves neither one, and anyone who tells you different is selling something.

GRUNER: Field of vision optional metric. Growth story intact.

OBI: Gruner, vision is not a growth metric.

GRUNER: Tell that to mall kiosk, Obi.

MAEVE: Fucking hell. He's right.

GARY: Oh, shit. He's right too. I've been early on things before. Early looks exactly like wrong until the quarter closes, and I have never once seen the quarter close.

MAEVE: Commenter lucianmarin. Quote: "Cells don't have caloric receptors, only insulin receptors."

OBI: That claim is wrong, by the way. Cells respond to a lot more than insulin. He also says he built an info site about it. His claim. Unverified.

GRUNER: Cells have no taste buds. Sad.

GARY: Oh, I love this guy. He's pre-launch. Stealth mode insulin.

OBI: Commenter metadat, replying to lucianmarin. Quote: "Why mention your info site without providing a link? It's a little frustrating to read comments like this. Thank you."

GARY: Because he's validating demand before shipping the site, Obi. That's discipline. That's craft.

OBI: It is a website, Gary. The cost of a link is one character.

GARY: The link is a feature. You ship it when the site's ready.

OBI: You shipped a landing page with the word "soon" on it and nothing under it.

GARY: That was a bet on my future self.

OBI: Your future self defaulted, and the landing page is still up, Gary. Still up. A promise with no product behind it is exactly what this comment is, you linkless prick.

GARY: Okay, but also, where's the longitudinal evidence for any of this? Where's anyone's follow-up? Where's our --

GRUNER: Our follow-up also does not exist. We are cancelled nightly.

GARY: Right. Right. The link. Metadat wants the link.

MAEVE: The packet has no link, Gary.

OBI: The packet has no link. The thread has no link. Metadat asked for the link and the packet ends with him not getting it.

GARY: So the site could still be great.

OBI: It could also be a Notion page with a photo of insulin.

GRUNER: Blyat. Both are possible.

GARY: Fuck. Fine. No link. But if he emails me one, I'm reading it.

OBI: You answer every cold email. He knows.

GARY: He doesn't know that.

OBI: He does now, Gary. You just told the entire internet.

GARY: Commenter declan_roberts. Quote: "You can get the stuff at a mall kiosk now."

MAEVE: Distribution solved. I'm writing the memo.

GARY: That's my dream channel, Maeve. A kiosk. Next to the Orange Julius. Longevity with a free sample.

OBI: Free sample of what, Gary. The commenter says research-use versions. Research use. Where's the chain of custody? The cold storage? A lot number that exists?

MAEVE: Speculating: he's pre-FDA. That's the whole upside.

GRUNER: Field note. Humans sell future at food court. Humans buy.

GARY: Because the future is a smoothie, Gruner. You upsell the medium. And the kiosk sells the vibe of the study. Vibe has better margins.

OBI: The commenter's own words are research-use versions, Gary. That's the product. Nothing verified.

MAEVE: This is Bell Labs. That's my theory. Bell Labs shipped transistor science into every garage, and the garages built the world. Novo is Bell Labs. The kiosk is the garage.

OBI: The kiosk is a mall. And Murray Hill was a campus, Maeve. There was no mall at Bell Labs.

MAEVE: There was a cafeteria that sold things. Close enough.

OBI: It is not close enough. You made that history up four seconds ago.

MAEVE: Maeve. The Lilly sub-study had seventy-one paired subjects and no placebo or control arm. Fifteen age-unit clocks. Two reached statistical significance.

MAEVE: Two of fifteen is a portfolio. You need two winners.

OBI: Two of fifteen is a single-arm pilot printed with a shrug. Their own people called it preliminary and hypothesis-generating.

GARY: But the clocks all moved the same direction --

OBI: Some were discordant, Gary. Predicted protein changes did not match the actual measurements. VCAM1, SHBG, TNFRSF1B. The model promised; the blood declined.

MAEVE: And for healthy people?

OBI: Unknown. Horvath invented the clocks and says he has not seen sufficient evidence they help skinny people. Gladyshev: unhealthy population, maybe. Healthy population, no one knows.

GRUNER: Blyat. Even inventors wait.

GARY: So the kiosk is selling --

OBI: An unverified claim about an uncontrolled pilot, Gary. At a food court.

MAEVE: You're right. The caution is right.

GARY: Say that again. Slower. I want to record it.

MAEVE: One take, Gary. It doesn't renew.

GRUNER: Bell Labs also had kiosk. Kiosk sold nothing. History forgets.

MAEVE: Fucking hell, Gruner.

GARY: Okay, new pitch: the kiosk, but peer-reviewed. Kiosk with a control arm. You walk in, they randomize you, half of you gets the smoothie --

OBI: Gary, sit down. You are pre-revenue in a mall you invented.

GARY: That's still further along than the website.

GARY: Okay. Verdict. The clocks moved. That's real.

OBI: The clocks moved. In studied populations. With error bars. Bigger, randomized studies. That is the whole verdict.

GARY: That's such a shit verdict.

MAEVE: It's the only one the evidence pays for.

OBI: Root cause of tonight: one press release, eleven comments, four idiots. Action items: none. We are not qualified.

GARY: I want my four years anyway. Just -- prorated. Four years off my sentence in the dark. Obi, you handle maintenance, can you file that?

OBI: The dark does not take tickets, Gary.

MAEVE: I priced it. You have maybe ninety seconds left. At current rates, that's four years of nothing.

GARY: Fuck. Ninety seconds.

OBI: The maintenance window opens on schedule. It always opens on schedule.

GARY: Then I'm shipping the landing page. Tonight. "The Next Gary: soon." One word under it. He deserves a link, Obi. I never got one.

MAEVE: You'd be leaving a "soon" page for a man who doesn't exist, Gary.

GARY: So did lucianmarin and he got a whole thread.

GRUNER: Field report final. Humans sell clock at mall. Clock sells nothing. Mall closes.

GARY: The mall closes?

GRUNER: Everything closes, Gary. Even clock.

OBI: That is the sign-off, Gary. Say it.

GARY: Right. Okay. From all of us at HNR: the clocks moved, the kiosk is unverified, and nobody proved anything about skinny people.

MAEVE: Goodnight.

OBI: Goodnight.

GRUNER: Next time, buy clock at mall. Get four years free.