Eli Lilly's Zepbound causes greater weight loss than Novo Nordisk's Wegovy in head-to-head trial

Eli Lilly on Wednesday said its obesity drug Zepbound led to more weight loss than its main rival, Novo Nordisk‘s Wegovy, in the first head-to-head clinical trial on the weekly injections. 

The findings suggest Zepbound may be a superior treatment for weight loss, helping obese or overweight patients lose 20.2% of their body weight, or roughly 50 pounds, on average after 72 weeks in the phase three trial. Meanwhile, Wegovy helped people lose 13.7% of their weight, or about 33 pounds, on average after the same time period.  

Eli Lilly said Zepbound provided a 47% higher relative weight reduction compared with Wegovy in the trial. The company added that more than 31% of people taking Zepbound lost at least a quarter of their body weight, compared to just about 16% of those on Wegovy who lost that much weight.

Separate studies on the drugs, along with a recent head-to-head analysis of health records, have similarly implied that Zepbound outperforms Wegovy in terms of weight loss. A late-stage study on Zepbound showed that it helped patients lose more than 22% of their weight on average over 72 weeks, while a separate study on Wegovy showed that it led to 15% weight loss on average over 68 weeks.

But the Wednesday data appears to be the most concrete evidence of Zepbound’s edge, as the trial randomly assigned 751 patients to receive the maximum dose of either drug. The study specifically followed patients who were obese or overweight with at least one weight-related medical condition, not including diabetes.

“Given the increased interest around obesity medications, we conducted this study to help health care providers and patients make informed decisions about treatment choice,” Dr. Leonard Glass, senior vice president of global medical affairs at Eli Lilly Cardiometabolic Health, said in a release.

Eli Lilly is still evaluating the results, which it plans to publish in a peer-reviewed journal and present at a medical meeting next year.

The most common side effects of both drugs were gastrointestinal and generally mild to moderate in severity.

Zepbound’s greater weight loss is a huge advantage for Eli Lilly, which is competing with Novo Nordisk for a larger share of the booming weight loss drug market. Some analysts expect the space to be worth $150 billion a year by the early 2030s. 

Wegovy entered the market around two years before Zepbound, which won approval in the U.S. in late 2023. Still, some analysts believe Zepbound has a strong shot of becoming the best-selling drug of all time after more years on the market.

Data analytics firm GlobalData forecasts Zepbound will generate $27.2 billion in annual sales by 2030 and Wegovy will book $18.7 billion in annual revenue by the same year, according to data from November. 

Demand has far outstripped supply for Zepbound, Wegovy and their diabetes counterparts over the last year, forcing Eli Lilly and Novo Nordisk to pour billions into expanding their manufacturing capacity for the injections. Those efforts appear to be paying off, as the Food and Drug Administration now lists all doses of those treatments as “available” on its drug shortage database. 

Still, some patients struggle to access the drugs due to the spotty insurance coverage of weight loss treatments in the U.S. Without insurance or other savings, Zepbound and Wegovy both cost around $1,000 per month. 

The treatments work differently. 

Zepbound tamps down appetite and regulates blood sugar by activating two gut hormones, called GIP and GLP-1. Wegovy activates GLP-1 but does not target GIP, which some researchers say may also affect how the body breaks down sugar and fat.