An experimental shot helped participants in a large trial lose far more weight than obesity drugs already on the market, Eli Lilly, the maker, announced on Thursday.
Among the heaviest patients in the trial, the results were on par with those seen with gastric bypass surgery, the only effective treatment for most with severe obesity.
The drug, retatrutide, appears to be the most powerful yet in a wave of injections and pills that have transformed the treatment of obesity — so much so that some participants in other research have said they stopped taking retatrutide because they felt they were losing too much weight.
If the drug’s effects do not wane with time, and if its results in the real world echo those in the clinical trial, it may extend the notion of what a weight loss drug can accomplish.
Eli Lilly reported the findings in a news release. The results have not yet undergone peer review or been published in a medical journal.
The drug’s powerful effects came at a cost. At higher doses, the drug often causes gastrointestinal side effects that are so unpleasant that some patients stop taking it.
Eli Lilly reported that 11 percent of participants who got the highest dose dropped out of the study because of side effects, higher than the figures seen with less powerful obesity drugs that are already available.
All of these drugs often cause side effects like nausea, vomiting, diarrhea and constipation, but those effects are rarely severe.
Eli Lilly has not yet applied for regulatory approval, but the drug has already generated intense interest.
As word has spread about promising results in Eli Lilly’s clinical trials, some Americans have been going online to order knockoff versions from China — alarming physicians and researchers, who are concerned that patients are not being monitored and could be harmed.
If approved, retatrutide would join an increasingly crowded market. Still, some doctors said they expected it might be most useful for the heaviest patients who are looking to lose the most weight and are reluctant to have bariatric surgery.
The results announced by Eli Lilly were from a randomized study of 2,339 patients who were obese or overweight. Those who got the highest dose of the drug had lost 70 pounds on average, or 28 percent of their body weight, after 80 weeks, the company said.
The drug led to even more weight loss in the heaviest patients in the study. Those with a body mass index over 35, considered moderate or severe obesity, were assessed after two years.
Over that time, those on the highest dose lost an average of 85 pounds, or 30.3 percent of their weight. By comparison, patients who have gastric bypass surgery lose about 30 to 35 percent of their body weight after two years.
The weight loss with retatrutide surpasses what is typically possible with the two most popular injections for obesity: Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy.
They can help people lose about 20 percent of their body weight over a similar period. Pill versions of the drugs deliver more modest weight loss, between 12 and 14 percent of body weight.
That is not enough for the 24 million Americans who have what is characterized as severe obesity, a body mass index of at least 40.
To reach a healthy weight, they need to lose 80 to 100 pounds, said Dr. Carolyn Apovian, an obesity specialist at Harvard Medical School.
Bariatric surgery usually can do it. But it has always been a hard sell, and the advent of effective obesity drugs has made it even less attractive for many patients. Demand for bariatric surgery has fallen as the obesity drugs have grown popular.
Eli Lilly hopes retatrutide can offer an alternative for very heavy patients. That group, in fact, was the initial target for the drug.
Dr. Daniel Skovronsky, the company’s top scientist, said he thought retatrutide might be most attractive to people who needed to lose large amounts of weight. But then he saw that the appeal might be broader.
The unexpected happened when patients took the lowest dose. More people taking the placebo dropped out of the study because of perceived side effects than people taking the active drug, Dr. Skovronsky said.
At that dose, participants lost about 19 percent of their weight, which is about what people lose with the highest dose of Zepbound. But retatrutide seemed surprisingly well tolerated.
Like Wegovy and Zepbound, retatrutide is injected once a week, and the dose is gradually increased, which minimizes gastrointestinal side effects.
The drug is a sort of a souped-up GLP-1, a class of drugs that has revolutionized the treatment of diabetes, obesity and other conditions.
It affects three hormones that help control appetite, energy balance and metabolism. They are GLP-1, which is the hormone modulated by Wegovy and Zepbound; GIP, targeted by Zepbound; and glucagon, a hormone that neither Wegovy nor Zepbound affects.
It is not clear to researchers why targeting these three hormones had a greater effect than the earlier medications that affect just one or two.
Dr. Ania Jastreboff, an obesity specialist at Yale who was principal investigator for the retatrutide study, said the study had “very impressive results, no doubt.”
But, she added, obesity is a chronic disease and what is important is not just the number of pounds lost.
Instead, she said, it is “the effects on a person’s health over their lifetime.”
For Eli Lilly, retatrutide is a chance to continue capitalizing on the weight loss drug craze. The company’s sales have boomed thanks to Zepbound, for obesity, and Mounjaro, for diabetes. Last fall, Eli Lilly became health care’s first company worth $1 trillion.
Eli Lilly sued the Food and Drug Administration in 2024, arguing that the agency had improperly classified retatrutide as a traditional drug, not as a biologic drug. The fight, which remains tied up in court, hinges on a highly technical dispute over how many amino acids retatrutide has in its chemical structure.
Getting the drug reclassified as a biologic could translate into billions of dollars for Eli Lilly, because it could block competitors and allow the company to charge higher prices for years longer than would otherwise be possible.
