Brian Reed: Hey. You see this Lilly thing come through?
Eliza Ward: Just opened it.
Brian Reed: So Eli Lilly announced results today — this is TRANSCEND-T2D-2, their Phase 3 head-to-head trial — and retatrutide, their new drug, produced somewhere around 20% body-weight loss versus 9.4% for Ozempic. In people with type 2 diabetes. Over 80 weeks.
Eliza Ward: More than double.
Brian Reed: More than double, yeah. 1,298 participants. And the A1C numbers — that's the blood sugar measure — retatrutide dropped it 2.2 percentage points, Ozempic 1.8. Both meaningful, but the weight gap is the one that's going to travel.
Eliza Ward: Wait — the comparator here is Ozempic at 2 mg. That's Novo Nordisk's drug, highest approved dose. That framing matters and I want to get to it. But just the raw number — 9.4 versus, what, 20.9 for the higher dose — that's genuinely striking even before you interrogate the methodology.
Brian Reed: Right — 19.5 for the 9 mg dose, 20.9 for the 12 mg. And the baseline weight was around 225 pounds, so we're talking close to 47 pounds lost on the high dose.
Eliza Ward: 47 pounds. Okay. That's the number that's going to be everywhere by tonight.
Brian Reed: But that 47-pound number — hang on — where exactly is it coming from? Because I saw something in the STAT News coverage about how the weight loss was reported.
Eliza Ward: That's the thing I flagged the second I read the press release. The weight-loss figures — the 19.5, the 20.9, all of it — those come from an on-treatment-completer analysis. Not intention-to-treat.
Brian Reed: Which means what, practically?
Eliza Ward: It means they only counted people who stayed on retatrutide for the full 80 weeks. If you dropped out — often because side effects got bad enough — you're just gone from the weight number. Think of it like a race where you only time the runners who crossed the finish line. The winner looks fast. But you've already cut everyone who cramped up and stopped.
Brian Reed: So the 20.9% isn't wrong — it's just, the population it describes is filtered. It's people who tolerated retatrutide well enough to stay.
Eliza Ward: Right — and that's actually a meaningful distinction, because if GI side effects are worse on a triple agonist than on a single-receptor drug like Ozempic, then your dropout rate could be higher, and the completers who remain are... I mean, they're a selected group. They might just be more tolerant patients.
Brian Reed: And the A1C number doesn't have that problem?
Eliza Ward: No — the A1C reduction, 2.2 percentage points for retatrutide versus 1.8 for Ozempic, that's on the full enrolled population. All 1,298 participants. So that signal is actually cleaner. The blood sugar result holds up better than the weight headline does.
Brian Reed: That comparator choice, though — the cleaner A1C number is almost beside the point now, because the take that's already circulating is 'retatrutide crushed the competition.' And the competition they chose was Ozempic. A drug Novo Nordisk got approved in 2017.
Eliza Ward: Six years old.
Brian Reed: Six years old. And Lilly already has tirzepatide — Mounjaro, Zepbound — on the market, and tirzepatide already beats Ozempic in its own trials. So why is Ozempic the comparator here and not their own drug?
Eliza Ward: There's a legitimate clinical answer and a strategic answer, and I think people are collapsing them. The legitimate part — Ozempic is still the most widely prescribed GLP-1 drug. Clinicians know it. It's the real-world baseline for a lot of patients. So comparing against it isn't — I mean, it's not fabricated.
Brian Reed: But it conveniently sidesteps the harder question.
Eliza Ward: Which is TRIUMPH-5. That's the Phase 3 trial Lilly launched that actually pits retatrutide against tirzepatide head-to-head. Those results don't exist yet. And Kenneth Custer's press release — he's the EVP who signed off on the announcement — doesn't mention that comparison once.
Brian Reed: Think about a hospital formulary committee meeting next month — actual pharmacists and physicians deciding whether to switch patients from Mounjaro to a newer, more expensive Lilly drug. The first question they ask is going to be: compared to what? And the answer is a drug from 2017.
Eliza Ward: Right — because if TRIUMPH-5 comes back showing tirzepatide performs comparably, then the case for replacing an already-approved, already-reimbursed Lilly drug basically collapses. That's the question today's announcement was very carefully not designed to answer.
Brian Reed: And honestly, the part that comes later in all of this — the stuff the trial results don't touch at all yet — that's the harder defense. We'll get there.
Eliza Ward: And the stuff the trial doesn't touch — I think about the SELECT trial. Because semaglutide has it. Ozempic has a cardiovascular outcomes trial. About a 20% reduction in major adverse events — heart attacks, strokes, deaths. That's a real evidence base. Retatrutide has nothing equivalent.
Brian Reed: Nothing? Like, not underway, or just... not done?
Eliza Ward: Not done. And the gap is that retatrutide will probably reach patients before that data exists. So a physician prescribing it — let's say a cardiologist covering a patient who had a mild MI last year, and they're also managing type 2 diabetes — they have no outcomes trial to point to. They're extrapolating from weight and A1C.
Brian Reed: Which is not nothing, but it's not SELECT.
Eliza Ward: It's not SELECT. And I want to be careful here — the absence of a CV outcomes trial isn't a flaw in retatrutide specifically, it's a structural timing issue. These trials take years. But it does mean we're genuinely in the dark on whether the weight loss translates to fewer heart attacks.
Brian Reed: The other piece — and this one surprised me when I dug into it — the 25% weight-loss figure that's been floating around, the one from the NEJM Phase 3 in September 2026. That's real, but it's from adults with obesity who don't have diabetes. TRANSCEND-T2D-2 enrolled people who do. Those aren't the same population, and I think the press release blurs that line pretty significantly.
Eliza Ward: Wait — yeah, that matters clinically. Because metabolic function in someone with type 2 diabetes is different. The drug may be working through partly different pathways. So taking the 25% figure and applying it to the diabetic trial results — I mean, that's the mental math everyone is doing and it's actually not valid.
Brian Reed: And the tolerability question ties into both of these. If GI dropout is high on retatrutide — and we don't know yet, the announced data doesn't resolve that — then the real-world weight loss shrinks, the on-treatment advantage becomes theoretical, and you've got a drug being adopted at scale before CV outcomes data and before tolerability is actually characterized.
Eliza Ward: So the thing to watch — concretely — is whether Lilly files an outcomes trial alongside its approval application, and what the FDA asks for as a post-market requirement. That's where the pressure lands. Not on today's numbers.
Brian Reed: And that's the same conclusion I'm at. TRIUMPH-5 is the actual test. Like, everything announced today — the TRANSCEND-T2D-2 numbers, the 20.9%, the A1C gap — all of it is framed against Ozempic, which means we're still waiting for the comparison that actually matters clinically. Retatrutide against tirzepatide. Until those results exist, I don't know how you make a confident prescription decision, let alone a formulary one. And retatrutide isn't even approved yet — it's still investigational. So we're debating the shape of a drug that isn't on shelves.
Eliza Ward: And the deeper problem — I mean, even if TRIUMPH-5 shows retatrutide beats tirzepatide on weight, that's still a proxy. Weight loss is not the same as surviving a heart attack. The SELECT trial proved that semaglutide reduces major cardiovascular events by about 20%. That took years and a dedicated outcomes trial. Retatrutide has no equivalent. So we're being asked to treat a better scale number as a clinical win, and that's... I don't think that's settled. It might be. But we don't know.
Brian Reed: Does more weight loss mean longer life? That's actually the question nobody can answer yet.
Eliza Ward: Not from this data. No.
