Retatrutide cut knee pain up to 75.8% in Phase 3, and the fine print matters
Lilly's first pivotal data for its triple-agonist drug lands at ACR this weekend just as Novo halves Wegovy's list price. The race has split between outcomes and price, and Lilly's headline percentages were never pre-specified.
Vincent Jiang · 4 min read
Knee pain fell by three quarters, and 1 in 8 patients ended the trial pain-free
Eli Lilly−0.93% — Eli Lilly, down 0.93 percent today published its first pivotal retatrutide data on November 5, one day before the American College of Rheumatology's annual meeting opens in Orlando on November 6 1. Retatrutide is Lilly's investigational once-weekly injection that activates three hormone receptors at once: GIP, GLP-1 and glucagon, the two hooks behind its tirzepatide drugs plus a third lever 1. It cannot be sold or marketed yet; the molecule remains investigational 1.
In TRIUMPH-4, a 68-week Phase 3 trial in adults with knee osteoarthritis and obesity, pain on the WOMAC scale, a standard osteoarthritis questionnaire, fell by up to 4.5 points, 75.8% from a 6.0 baseline, and more than 1 in 8 patients ended the trial reporting no knee pain 1.
In the 80-week TRIUMPH-1 trial, pain fell up to 4.3 points (73.1%), with more than 1 in 6 ending pain-free 1. Those "up to" percentages are post-hoc slices; the pre-specified means are lower, and the plenary showing the full dataset lands Sunday November 8 at 11:15 a.m 1. EST 1.
The stakes: a $24.4 billion quarter against a halved Wegovy price
The commercial context is a market splitting in two. Lilly's third-quarter revenue reached $24.4 billion, up 39% 2, and full-year guidance rose to $91 billion to $92 billion 3. With about 80% of knee osteoarthritis patients carrying obesity or overweight 1, Lilly is pitching an obesity drug into orthopedic pain, not just weight.
Novo Nordisk−0.30% — Novo Nordisk, down 0.30 percent today answered with price: Wegovy's US list price drops about 50% to $675 a month from January 1, and the Wegovy pill pulled in $810 million in the third quarter, up 53% from the second 4. Novo claims 80% of new oral GLP-1 starts; Lilly says its rival pill, Foundayo, took 40% 2.
The fine print: the headline percentages were never pre-specified
Lilly's own endnote states that percent change in the WOMAC pain score was not pre-specified and was estimated from a post-hoc analysis 1. The peer-reviewed TRIUMPH-1, published in NEJM on October 29, shows the mean: at the top 12 mg dose, pain fell 3.6 points versus 1.9 on placebo, a 61.6% reduction, with 25% weight loss 5. The release's "up to" figures are the most flattering slice of each trial, and the 75.8% and 73.1% in the first section above are that same post-hoc metric 5.
The psoriatic arthritis numbers carry the same caution. The 52-week comparison of 43.7% ACR50, the standard rheumatology bar for at least 50% improvement, for Taltz, Lilly's immunology drug, plus Zepbound versus 15.7% on Taltz alone, is exploratory with no multiplicity control 1.
Peer-reviewed TRIUMPH-1: 3.6 points of pain relief at the top dose, 1.9 on placebo
The peer-reviewed mean at 12 mg is 3.6 points; the release headline says up to 4.3
Data
| Value | |
|---|---|
| Placebo | 1.9 pts |
| 4 mg | 3.2 pts |
| 9 mg | 3.5 pts |
| 12 mg | 3.6 pts |
Novo's counter: 8 million prescriptions and a 30% price slide
Novo's pill has filled 8 million cumulative prescriptions since its January launch 24. Its 80% share claim leans on telehealth channels such as Hims & Hers that do not report to IQVIA−0.25% — IQVIA, down 0.25 percent as of its last quote 2. "Those companies do not share their data with IQVIA," said Novo CEO Mike Maziar Doustdar, who says IQVIA covers only 65% of Novo's scripts 2. Lilly's 40% rests on IQVIA 2. Neither number is audited 2.
A 30% price slide, and the operating-room argument
Novo's share claim also sits beside erosion: net Wegovy price fell 30.35% in the quarter 6. Foundayo booked $184 million in third-quarter sales, short of analyst expectations 3. A function-priced drug also walks into an argument orthopedists are already having: a June database study found three years on Wegovy or Zepbound was associated with about 5 fewer knee replacements per 100 people over 8 years, out of roughly 800,000 US knee replacements a year, though it is observational and cannot prove the drugs caused it 7.
"Anything that reduces pain, including weight loss, can defer or avoid an operation without changing the underlying arthritis at all," as Stanford orthopedic surgeon Derek Amanatullah put it 7.
The share war: Novo claims 80% of new oral starts, Lilly claims 40% for Foundayo
Neither Q3 share claim is audited: telehealth scripts sit outside IQVIA's count
Data
| Value | |
|---|---|
| Wegovy pill, Q1 | 65% |
| Wegovy pill, Q3 | 80% |
| Foundayo, Q3 | 40% |
What to watch on Sunday
Three tells decide the next leg. Whether the full TRIUMPH-4 dataset shown at the plenary holds up the post-hoc percentages 1. Whether Lilly files retatrutide on a function claim rather than weight alone, which is what a payer would have to underwrite. And whether Novo's January price cut holds its share once Foundayo reaches more pharmacies 4.
Retatrutide cannot be sold yet, and a Phase 3 readout is not a coverage decision 1. But the first non-weight indication has printed: Novo is cutting price to win patients, and Lilly just printed data meant to win payers.
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