An experimental injection helped participants in a large trial lose significantly more weight than anti-obesity drugs already on the market, manufacturer Eli Lilly announced Thursday.
Among the most overweight patients in the trial, results were on par with those seen with gastric bypass surgery, the only effective treatment for most of those with severe obesity.
The drug, retatrutide, appears to be the most powerful yet in a wave of injections and pills that have transformed obesity treatment, so much so that some participants in other research said they stopped taking retatrutide because they felt they were losing too much weight.
If the drug’s effects do not wane over time, and if its real-world results are similar to those in the clinical trial, this can broaden the notion of what a weight loss drug can achieve.
Eli Lilly reported the findings in a press release. The results have not yet been peer-reviewed or published in a medical journal.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 received the highest dose dropped out of the study due to side effects, higher than those seen with less potent anti-obesity drugs already available.
All of these medications usually cause side effects such as nausea, vomiting, diarrhea, and constipation, but these effects are rarely serious.
Eli Lilly has not yet filed for regulatory approval, but the drug has already generated significant interest.
As word spread about promising results from Eli Lilly’s clinical trials, some Americans have been ordering knock-off versions from China online, alarming doctors and researchers who are worried that patients are not being monitored and could be harmed.
If approved, retatrutide would join an increasingly saturated market. Still, some doctors said they hoped it might be most helpful for heavier patients who are looking to lose the most weight and are reluctant to undergo bariatric surgery.
The results announced by Eli Lilly come from a randomized study of 2,339 obese or overweight patients. Those who received the highest dose of the drug had lost an average of 70 pounds, or 28 percent of their body weight, after 80 weeks, the company said.
The drug caused even greater weight loss in the heaviest patients in the study. Those with a body mass index greater than 35, considered moderate or severe obesity, were evaluated after two years.
During that time, those who received the highest dose lost an average of 85 pounds, or 30.3 percent of their weight. In comparison, patients who undergo gastric bypass surgery lose 30 to 35 percent of their body weight after two years.
Weight loss with retatrutide exceeds what is typically possible with the two most popular obesity injections: 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 produce a more modest weight loss, between 12 and 14 percent of body weight.
That’s not enough for the 24 million Americans who suffer from what is characterized as severe obesity, a body mass index of at least 40.
To reach a healthy weight, they need to lose between 80 and 100 pounds, said Dr. Carolyn Apovian, an obesity specialist at Harvard Medical School.
Bariatric surgery can usually achieve this. But it has always been a tough sell, and the arrival of effective anti-obesity drugs has made it even less attractive to many patients. Demand for bariatric surgery has fallen as obesity medications have become popular.
Eli Lilly hopes that retatrutide can offer an alternative for heavy patients. That group, in fact, was the initial target of the drug.
Dr. Daniel Skovronsky, the company’s top scientist, said he thought retatrutide might be more attractive to people who needed to lose large amounts of weight. But then he saw that the appeal could be broader.
The unexpected happened when the patients took the lowest dose. More people who took the placebo dropped out of the study because of perceived side effects than people who took the active drug, Dr. Skovronsky said.
At that dose, participants lost about 19 percent of their weight, which is about what people lose on 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 increased gradually, minimizing gastrointestinal side effects.
The drug is a type of improved 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. This is GLP-1, which is the hormone modulated by Wegovy and Zepbound; GIP, Zepbound target; and glucagon, a hormone that neither Wegovy nor Zepbound affects.
It’s not clear to researchers why targeting these three hormones had a greater effect than previous drugs that affected only one or two.
Dr. Ania Jastreboff, a Yale obesity specialist and principal investigator of the retatrutide study, said the study had “very impressive results, for sure.”
But, he added, obesity is a chronic disease and what is important is not only the number of kilos lost.
Rather, he said, they are “the effects on a person’s health over the course of their life.”
For Eli Lilly, retatrutide is an opportunity to continue taking advantage of the weight-loss drug trend. The company’s sales have skyrocketed thanks to Zepbound, for obesity, and Mounjaro, for diabetes. Last fall, Eli Lilly became the first $1 trillion healthcare company.
Eli Lilly sued the Food and Drug Administration in 2024, arguing that the agency had incorrectly classified retatrutide as a traditional drug, not a biologic drug. The fight, which remains stuck in court, revolves around a highly technical dispute over how many amino acids retatrutide has in its chemical structure.
Reclassifying the drug as a biologic could translate into billions of dollars for Eli Lilly, because it could lock out competitors and allow the company to charge higher prices for years longer than would otherwise be possible.
