A Next-Generation Drug Causes Dramatic Weight Loss, Eli Lilly Says

Eli Lilly is reporting promising results for the first drug to target three hormones related to weight loss—not just one or two, as current GLP-1 drugs do. In a press release, the company reported that its experimental injectable drug, retatrutide, helped people who were overweight or obese to lose up to 28% of their body weight over 1.5 years compared to people receiving placebo.

That’s on par with weight loss associated with bariatric surgery, says Kenneth Custer, executive vice president at Lilly and president of cardiometabolic health.

The results add to previous findings on retatrutide among people with obesity and diabetes, which showed that the drug helped them lose 16.8% of their body weight compared to those taking placebo, in addition to lowering their blood sugar. The current study did not include people who had diabetes, to specifically determine how effective the drug is in addressing obesity.

The new trial tested three doses of the drug that people injected once a week, and those randomly assigned to take the lowest dose—4 mg—lost about 19% of their body weight during the study period compared to those taking placebo. That’s similar to the amount of weight people lose while taking the highest dose of another Lilly drug, Zepbound (tirzepatide), for about a year. Zepbound targets two weight-related hormones, GLP-1 and GIP, while retatrutide targets those two plus glucagon.

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The data on retatrutide—which is not yet approved by the U.S. Food and Drug Administration (FDA)—raise the question of what role each of the growing number of drugs in this category will have in managing obesity, and whether some may become redundant. The medications come in injectable form (Wegovy and Zepbound) as well as in pills (Wegovy pill and Foundayo). Side effects are an important factor in how people chose a weight-loss medication, and while all of the drugs in this category come with GI-related side effects including nausea, vomiting, and diarrhea, some people experience more severe symptoms than others on certain drugs. In the current study, about 11% of people on the highest dose of retratutide stopped taking the drug because of the side effects, which is about the same rate as those who dropped out of the tirzepatide studies that Lilly conducted. Real-world studies show the drop-out rate may be slightly higher, at about 15%.

Another important factor involves the additional health benefits patients may receive from the drugs. Novo Nordisk’s drug Wegovy, for example, is approved not just for weight loss but also to lower the risk of heart events and liver conditions, while Zepbound is approved to reduce the risk of sleep apnea. Both companies are continuing to study their products for additional potential health benefits for the kidneys, arthritis, and substance-abuse disorders. Custer says Lilly is conducting further studies on retatrutide to better understand whether the triple-acting drug benefits health in other ways as well.

He says Lilly is also comparing tirzepatide and retatrutide directly and expects to have results from that study toward the end of 2026 or beginning of 2027, which could provide information for doctors and patients about which option might be most suitable. “Right now, it seems both medicines are future mainstays in the treatment of obesity,” he says. “And we’re fine to be competing with ourselves.”