Eli Lilly's Zepbound defeats Novo Nordisk's Wegovy in head-to-head weight loss trial

Over the last two-plus years, as Eli Lilly and Novo Nordisk have battled for their share of the massive weight loss market and patients wondered which company’s products were more effective, there were constant reminders that there was no definitive answer until the compounds were pitted in a head-to-head clinical trial.

Wednesday, the answer finally arrived as Lilly revealed results from a study that showed that its obesity drug Zepbound was 47% more effective than Novo’s Wegovy in helping patients lose weight.

In the SURMOUNT-5 study, while participants taking Zepbound lost an average of 20.2% of their weight after 72 weeks, those on Wegovy lost 13.7% of their weight. The results translated to an average weight loss of 50.3 pounds (22.8 kg) for patients on Zepbound and 33.1 pounds (15 kg) for those taking Wegovy.

Additionally, in a key secondary endpoint, 32% of people taking Zepbound achieved at least a 25% body weight loss compared to 16% of those on Wegovy.

The study included 751 participants in the U.S. and Puerto Rico who were overweight or obese, had at least one weight-related medical problem and did not have diabetes. They were randomized 1:1 to receive the maximum tolerated dose of Zepbound or Wegovy. 

“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, M.D., Lilly’s vice president of global medical affairs/cardiometabolic health, said in a release.

The results weren't a major surprise as separate clinical studies on tirzepatide and semaglutide had already suggested that Lilly’s drug was more effective in helping patients lose weight. While Lilly’s trial that led to the approval of Zepbound showed an average body weight loss of 21% over 72 weeks, Novo’s study for Wegovy produced an average weight loss of 15% through 68 weeks.  

The results of SURMOUNT-5 should help differentiate the company’s products, which often are mistakenly lumped together as glucagon-like peptide-1s (GLP-1s). While Novo’s semaglutide regulates the GLP-1 incretin hormone, Lilly’s tirzepatide acts on both the GLP-1 and the gastric inhibitory polypeptide (GIP) hormones. Both are involved in the production of insulin and the control of appetite.

The results also should help Lilly reduce Novo’s edge in the market. In the third quarter, while Novo reported combined sales of Wegovy and diabetes treatment Ozempic at $6.8 billion, Lilly said that Zepbound and its diabetes drug Mounjaro generated combined sales of $4.4 billion.

A large part of the advantage for Novo was that it was first to market with both Ozempic and Wegovy, which were approved in 2017 and 2021, respectively, compared to Mounjaro (2022) and Zepbound (2023).

Lilly and Novo should have the market to themselves for a while. Viking Therapeutics could be first to join the competition after posting promising results in a phase 2 trial of its GLP-1/GIP candidate earlier this year.

“Competition in the obesity field is expected to intensify toward the end of this decade, as many companies have treatments in development expected to launch in the late 2020s,” according to Costanza Alciati, an analyst at GlobalData.