The battle for market share between the two leaders in the booming obesity drug sector has a new data point decidedly in favor of Eli Lilly. The Lilly drug Zepbound has topped Novo Nordisk’s Wegovy in a head-to-head clinical trial.
According to the preliminary Phase 3b results, treatment with Zepbound led to 47% greater relative weight loss compared to Wegovy, Lilly announced Wednesday. The pharmaceutical giant said more details will be published and presented at a medical meeting next year. But these results provide evidence that a drug that hits two metabolic targets leads to greater reduction in weight, which could give Lilly an edge as it seeks gains in market share and insurance coverage of the blockbuster product.
Zepbound’s main ingredient is a peptide engineered to bind to and activate two targets, the GLP-1 and GIP receptors. By contrast, Novo Nordisk’s Wegovy targets only the GLP-1 receptor. Both drugs are administered as once-weekly injections.
The head-to-head test enrolled 751 people in the U.S. and Puerto Rico with obesity or overweight as well as certain associated comorbidities, such as hypertension and cardiovascular disease. However, the study specifically excluded those who have type 2 diabetes. Participants were randomly assigned to receive Zepbound or Wegovy for 72 weeks. The main goal was to measure the percent change in body weight from baseline.
Participants in the Zepbound cohort showed an average 20.2% loss in body weight, Lilly said. That translates to an average 22.8 kg (50.3 pounds) of weight shed. By comparison, those who received Wegovy lost an average 13.7% of their weight, or 15 kg (33.1 pounds). On a key secondary endpoint, Lilly said 31.6 % of participants receiving Zepbound achieved at least 25% body weight loss. In the Wegovy arm, 16.1% of participants achieved that mark.
“Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice,” Leonard Glass, senior vice president of global medical affairs at Lilly Cardiometabolic Health, said in a prepared statement.
Lilly said the overall safety profile of Zepbound in the head-to-head study was similar to previous tests of its drug. This entire of drugs that mimic gut hormones comes with gastrointestinal side effects that lead some patients to discontinue treatment. The Phase 3 clinical trial results that supported Zepbound’s FDA approval last year showed side effects such as nausea, diarrhea, and vomiting. Lilly said the Wednesday that the most commonly-reported adverse events in Zepbound’s Phase 3 program were gastrointestinal and were classified as mild to moderate in severity.
Zepbound has fast become one of Lilly’s top products. In the nine months ended Sept. 30, Lilly reported more than $3 billion in Zepbound sales. The latest clinical trial results should help Zepbound gain market share over Wegovy, Leerink Partners analyst David Risinger said in a Wednesday note sent to investors. But he pointed out that Lilly did not disclose a comparison of the tolerability of these medications, which could be another point of differentiation beyond the magnitude of weight loss. A cross-trial comparison of historical data from independent Phase 3 tests of each medication showed better tolerability for Zepbound compared to Wegovy, with the Novo Nordisk product posting higher rates of nausea and vomiting, Risinger said. He added that he’s looking forward to the publication and presentation of the head-to-head data in 2025 for more details on this comparison.
There are other companies developing weight loss drugs that target both GLP-1 and GIP. Viking Therapeutics has reached Phase 3 testing with VK2735, a once-weekly injectable medication designed to activate both the GLP-1 and GIP receptors. Viking could stand apart from the field with an oral version, which last month posted encouraging Phase 1 data.
Amgen is also going after both GLP-1 and GIP with a drug called MariTide. But one key difference with Amgen’s drug is that rather than activating the GIP receptor, the peptide antibody conjugate blocks this target. Last week, Amgen reported preliminary Phase 2 results showing MariTide achieved weight loss comparable to Lilly’s Zepbound. Amgen aims to differentiate with once-monthly or even less frequent dosing.
Lilly isn’t settling for just two targets. It’s R&D efforts include retatrutide, a peptide engineered to hit GLP-1, GIP, and a third target — the glucagon receptor. Last year, Lilly reported Phase 2 results showing this triple mechanism achieved greater weight reduction than GLP-1 and GIP activation. Results were published in the New England Journal of Medicine. Retatrutide’s late-stage clinical development includes tests underway in obesity and type 2 diabetes.
Photo by Eli Lilly
