Which Weight-Loss Drug Is Better: Wegovy or Zepbound?

With more people taking the weight-loss drugs Wegovy and Zepbound, one question inevitably arises: which one is more effective?

In a press release, Lilly announced that in its latest trial comparing its medication, Zepbound, to Wegovy, made by Novo Nordisk, people randomly assigned to receive Zepbound lost about 20% of their body weight after about 18 months, while those taking Wegovy lost nearly 14% of their body weight.

Wegovy (semaglutide) and Zepbound (tirzepatide) both target a group of hormones that the body makes called incretins. Wegovy works on the GLP-1 hormone, which suppresses appetite and signals the pancreas to produce insulin to break down sugars in food. Zepbound works on both GLP-1 and GIP, another hormone that stimulates insulin production. Separate studies conducted by the respective manufacturers have showed that Zepbound, with its dual-acting effect, was linked to more weight loss than Wegovy, but until now, no studies have compared the two medications directly. Lilly's chief scientific and medical officer, Dan Skovronsky, says the company conducted the trial to clear up confusion about the differences between the drugs and questions doctors and patients had about which medication to use and whether one was "better" than the other. "Now we have head-to-head data to add to that conversation, and we've shown that Zepbound gives superior weight loss," he says.

The study also showed that people taking Zepbound reported less vomiting, one of the side effects of the medications, which Skovronsky says may be due to GIP, which works in the brain to suppress nausea.

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In a statement, a spokesperson for Novo Nordisk focused on the other health benefits of its semaglutide medication. "In combination with diet and exercise, Wegovy is the only proven obesity medicine proven to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and with either obesity or overweight," the company said. In March, the U.S. Food and Drug Administration allowed the company to add on Wegovy's label that the drug can lower the risk of heart events in people with heart disease who are overweight or obese. "As a pioneer and leader in obesity care, we know that treating this misunderstood disease is more than just a number on a scale, and we strongly believe in the semaglutide molecule and the robust data supporting its benefits." Novo Nordisk is continuing to study semaglutide for its potential benefits in other conditions, from Alzheimer's disease to kidney and liver conditions.

Lilly is also studying the other health benefits of tirzepatide and has published studies showing that the drug can lower the risk of heart failure and death from heart disease, as well as reduce sleep apnea and help people avoid progressing from prediabetes to diabetes. The company plans to publish these latest findings in a peer-reviewed journal and present them at a medical conference next year after analyzing them more fully.

The results are in line with past studies each pharmaceutical company conducted to earn approval from the U.S. Food and Drug Administration, but the direct comparison could encourage more development of medications that target multiple hormones, in order to achieve greater weight loss and potentially other health benefits. Lilly is developing a drug that targets three hormones: the two incretin hormones, GLP-1 and GIP, and glucagon. Both companies are also finding ways to put the medications, which patients currently need to inject, into pill form.