Novo Nordisk recently sued Lilly, claiming that some Lilly ads misleadingly present Zepbound (Lilly’s drug tirzepatide) as causing significantly more weight loss than Wegovy (Novo’s drug semaglutide). What’s in contention in this case, and what does the scientific evidence say?
Lilly began running ads claiming that “people using Zepbound lost an average of 50 pounds compared to an average of 33 pounds with up to a 2.4 mg dose of the Wegovy injection.” The numbers that Lilly’s ad uses come from a clinical trial called SURMOUNT-5 that randomized patients to tirzepatide or semaglutide, increasing each participant’s dose to their maximum tolerated dose (10 or 15 mg for tirzepatide and 1.7 or 2.4 mg for semaglutide). At 72 weeks, average weight loss was 20.2% with tirzepatide and 13.7% with semaglutide.
In March 2026, the FDA approved a new, higher dose (7.2 mg) of Wegovy. Novo argues that this approval renders Lilly’s comparison in the ads outdated and says that the ads have misled consumers and caused commercial harm.
Legality of advertising claims aside, what does a valid older head-to-head trial scientifically allow you to claim after one of the drugs gains a more effective dose?
As an analogy, let’s imagine two marathon runners, Z and W. Runner Z ran several minutes faster than runner W when they originally competed against each other in the same marathon. Later, runner W set a new personal best on a different course. W’s new result may change your expectations of how fast W can run, but it can’t tell you who would win a rematch.
The strongest evidence supporting Lilly’s position is the head-to-head randomized trial. Randomization placed both drugs under the same conditions, with the same patient population, the same lifestyle program, follow-up period, and statistical analysis. Within those conditions and at the doses tested, tirzepatide clearly came out on top for average weight loss.
From Novo’s standpoint, that ignores the fact that there is now a higher approved dose of Wegovy than what was compared in the head-to-head. Novo’s new trial, called STEP UP, compared the 7.2 mg dose of Wegovy to the previous highest 2.4 mg dose of Wegovy, with the 7.2 mg dose coming out with significantly more weight loss (18.7% with 7.2 mg and 15.6% with 2.4 mg). That is new information that the SURMOUNT-5 comparison did not address. However, STEP UP did not directly compare semaglutide and tirzepatide.
Complicating all of this is how you can get the highest dose of each of the drugs. For Zepbound, its label (prescribing instructions) says you can be gradually escalated to the highest dose as a standard maintenance dose. For Wegovy, however, the highest dose (7.2 mg) is conditional on someone having tolerated the next highest dose for 4 weeks as well as having a clinical indication for additional weight loss. That arguably makes the head-to-head trial a fairer comparison based on the prescribing information.
Which is fairer: comparing the highest approved doses of two drugs, or putting both drugs in the same clinical trial (on the same “race course”)? The STEP UP results narrow what Lilly can claim in its ad based on the scientific evidence. It can still say that Zepbound produced more weight loss in the head-to-head trial that was run (SURMOUNT-5), but it can’t scientifically make the broader claim that it produces significantly more weight loss than every approved Wegovy regimen. Conversely, STEP UP doesn’t prove that Wegovy at the new highest dose matches or beats Zepbound. That direct comparison requires a new head-to-head clinical trial. Whether that makes Lilly’s ad misleading from a legal standpoint, and what damages there might be, is up to a court to decide.
What framework can we take away from this case? When you are judging a comparison of two drugs, ask these questions:
Is the comparison based on a head-to-head (same trial) or cross-trial comparison (separate trials for each drug)?
If it was a cross-trial comparison, were the durations, patient populations, and estimands (including how treatment discontinuation was handled) close enough to be compared?
What exact doses and regimens of each drug were tested?
Where do these doses sit in the prescribing labels of each drug? Are they standard maintenance doses or do they require conditional escalation?
If a claim is being made about the comparison, does the claim stay within the doses, population, time point, and outcome that the evidence actually tested?
The GLP-1 Verdict is my attempt to make these choices visible. I use a consistent method to compare approved obesity drugs, selecting evidence that matches as closely as possible across trial dose, duration, indication, patient population, and statistical analysis. For Zepbound and Wegovy, that means I show SURMOUNT-5 as the direct head-to-head result and treat the Wegovy 7.2 mg evidence separately, because the newer dose has not yet been tested directly against Zepbound.
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