Lilly says Zepbound beat Wegovy HD by 4.5%; on its second measure the gap is 1.8% and not statistically significant

Eli Lilly said on Tuesday that its obesity drug Zepbound, at the 10 mg and 15 mg doses, was associated with more weight loss than Novo Nordisk's Wegovy HD, the 7.2 mg version of semaglutide, according to the company's press release. The results were presented at the European Association for the Study of Diabetes annual meeting. MarketWatch and RTTNews both headlined the result as a Zepbound win.

What kind of comparison this is

This was not a trial of the two drugs against each other. It is an indirect treatment comparison: Lilly took results from its own SURMOUNT-1 study of Zepbound and from Novo's STEP UP program for Wegovy HD, then adjusted for sex, age, starting weight and starting blood sugar. Lilly's release says so itself: "In the absence of a head-to-head trial comparing tirzepatide 15 mg against semaglutide 7.2 mg, this indirect comparison offers useful evidence."

Lilly does have a real head-to-head study, SURMOUNT-5, but that one tested Zepbound against the older Wegovy doses of 1.7 mg and 2.4 mg. In it, Zepbound users lost 20.2% of body weight at 72 weeks against 13.7% for Wegovy. Wegovy HD is Novo's higher dose, which it launched in the U.S. in April.

The number that shrinks

The headline 4.5% figure comes from what trials call the treatment-regimen estimand, which counts everyone who started the drug, including people who stopped. The release also reports the efficacy estimand, which looks at people who stayed on treatment as intended. On that measure:

Read together, the gap depends heavily on how dropouts are counted. Among people who stayed on the drugs, the difference in average weight loss was small enough that the analysis could not rule out no difference at all. The odds figures are real, but their ranges run from barely above even to more than ten times, which is what happens when two separate trials are stitched together. Lilly said discontinuation rates due to side effects were comparable.

The market read it the same way

Lilly shares were at $1,188.99 before the open, up 0.4% from Monday's $1,184.78, and Novo's U.S. shares were down 1.3% at $38.22, according to Nasdaq data.

Who it actually reaches is doctors and the people who pay. Employer health plans and pharmacy benefit managers decide which GLP-1 drug is preferred on a formulary, weighing price alongside results. A 1.8-point difference that is not statistically significant gives a plan little reason to change its choice; a 4.5-point one is the figure Lilly's sales teams will lead with. The head-to-head trial against Wegovy HD that would settle it has not been run.

Sources: Eli Lilly press release; RTTNews; MarketWatch; Nasdaq quote data (premarket, 8:56 a.m. ET); Lilly filings on SEC EDGAR. This is market information, not investment advice.