SAN DIEGO — An experimental drug from Eli Lilly has the potential to provide greater weight-loss benefits than any drug currently on the market.
The experimental drug, retatrutide, helped people lose, on average, about 24% of their body weight, the equivalent of about 58 pounds, in a mid-stage clinical trial, the company said Monday from the American Association of Diabetes. annual meeting in San Diego. The findings were simultaneously published in The New England Journal of Medicine.
If the results are confirmed in a largest phase 3 clinical trial – expected to be in operation until the end of 2025 – retatrutide could overtake another Lilly weight-loss drug, tirzepatide, which experts estimated earlier this year could become the best-selling drug of all time. Tirzepatide is currently approved for type 2 diabetes under the name Mounjaro; The FDA is expected to approve the weight-loss drug this year or early next year.
The new findings, according to Dr. Shauna Levy, an obesity medicine specialist and medical director of the Tulane Bariatric Center in New Orleans, are «mind-boggling.»
Levy, who was not involved in the research, said the drug appears to be yielding results that approach the effectiveness of bariatric surgery. «It’s certainly knocking on the door or reaching out,» he said.
More about weight loss drugs
The new study underscores the rapid rise in recent years in the discovery of new weight-loss treatments as companies invest in a new class of drugs called GLP-1 agonists, which mimic a hormone that helps reduce the intake of food and appetite.
The drugs have been «transformational to say the least,» Levy said. «They have given hope to so many people who feel a little helpless in this fight against the disease of obesity.»
Semaglutide, the active ingredient in Novo Nordisk’s popular drugs Ozempic and Wegovy, is a GLP-1 agonist. Lilly’s tirzepatide acts as a GLP-1 agonist and also mimics another hormone called GIP.
Retatrutide mimics GLP-1 and GIP, as well as another hormone, glucagon. GIP is believed to improve the way the body breaks down sugar; glucagon can reduce appetite and help metabolism work more efficiently.
“This may explain why retatrutide produces more effective weight loss,” said Dr. Holly Lofton, director of NYU Langone Health’s weight management program. She was not involved in the trial, although she previously served on an advisory board for Ozempic and Wegovy’s maker, Novo Nordisk.
Dr. Dan Skovronsky, Eli Lilly’s chief scientific and medical officer, told NBC News that rettrutide attempts to tap into the body’s own mechanisms that metabolize food and tell the body when to stop eating.
«We’ve taken those normal signaling molecules in your body and turned them into drugs,» Skovronsky said.
How does retatrutide compare to other weight loss drugs?
Lilly’s phase 2 trial enrolled 338 overweight or obese adults and they were randomized to receive either a placebo or one of four doses of retatrutide. The drug was administered as a weekly injection.
The participants had a body mass index, or BMI, of 27 or higher. The results published Monday did not include patients with type 2 diabetes, a group who are also prescribed GLP-1 drugs because of their effects on blood sugar levels. TO separate trial is looking at retatrutide for patients with type 2 diabetes.
After 24 weeks, patients taking the highest dose (12 milligrams) lost an average of 17.5% of their body weight, the equivalent of an average of 41 pounds, according to the company. At 48 weeks, the weight loss increased to 24.2% of her body, or 57.8 pounds.
«The degree of efficacy was definitely surprising,» said Dr. Ania Jastreboff, an obesity medical scientist at Yale University School of Medicine and lead author of the phase 2 study.
What’s more, at the end of 48 weeks, their weight loss had not yet plateaued, meaning they potentially could have lost even more weight if they had continued taking the drug for a longer period of time, he said.
Jucynthia Jessie, 44, of Laplace, Louisiana, participated in the trial and lost 60 pounds.
“I was totally shocked,” Jessie said. «You don’t know if you have the placebo or not, so once I started seeing the results, no one told me any different, but I saw the results myself and was really surprised.» (Jessie wasn’t told the trial was looking at rettrutide, just that it was a study on a weight-loss drug, but the research center confirmed this with NBC News.)
He’s gained about 15 pounds in the nine months since completing the trial, but said he still believes the weight loss is sustainable with healthy lifestyle choices.
Weight loss in the trial appeared to occur faster than with other weight-loss drugs, according to Jastreboff. Novo Nordisk Semaglutide was found to reduce body weight, on average, about 15%, or about 34 pounds, after 68 weeks. And Lilly’s other weight-loss drug, tirzepatide, was shown to reduce body weight, on average, by 22.5%, or about 52 pounds, after 72 weeks. These are certainly not head-to-head comparisons because the drugs were not compared in a head-to-head clinical trial.
Dr. Fatima Cody Stanford, an obesity physician at Massachusetts General Hospital in Boston, said that when patients lose weight very rapidly — more than 10 pounds a month — they may be at risk of developing gallstones. It’s a known side effect after bariatric surgery, she said, and it would be something she would watch out for. In clinical trials, tirzepatide and semaglutide they have also been associated with a small but slightly increased risk of gallbladder disease, including gallstones.
The speed of weight loss seen with retatrutide was not a concern to Lofton. Rapid weight loss is generally only harmful «if achieved in an overly restrictive way, such as drinking only water or eating only cabbage,» he said.
Still, he said he wanted to see more data on the amount of lean body mass — that is, the weight in the body that isn’t fat, including muscle and bone organs — that people lose on the drug. Losing too much lean mass can cause a person’s metabolism to slow down.
The side effects of retatrutide were similar to those of other weight-loss drugs, Skovronky said. Side effects of Ozempic and Wegovy, for example, include nausea, vomiting, diarrhea, and constipation. In general, people experience these side effects as they increase the dose at the beginning of treatment, but the side effects usually go away after prolonged use.
Who would retatrutide be for?
Although the FDA is expected to approve Lilly’s other weight-loss drug, tirzepatide, in the coming months, Skovronksy said he believes it can coexist with retatrutide.
“We don’t stop with a drug for Alzheimer’s disease,” he said. «The same will be true for metabolic diseases, including obesity and type 2 diabetes. We will need different types of drugs for different patients.»
Jastreboff agreed. Retatrutide could be an option for people who do not respond well to other weight loss drugs. Given its potency, it could also be useful for people who need to lose a substantial amount of weight, he said.
Still, retatrutide has a long way to go before it’s available to the public.
“It’s early,” Skovronsky said. The company has begun enrolling participants in a larger Phase 3 clinical trial, which will include thousands of participants. The trial is expected to conclude in December 2025, according to clinical trials.gov. After that, if the results hold up, the drug will have to go through the FDA’s rigorous review process.
Skovronsky said that he hopes that retrutation may one day provide the same levels of weight loss seen with bariatric surgery.
He also said that retatrutide and similar drugs could be used to treat obstructive sleep apnea, as well as lower the risk of heart disease.
“This is truly a golden age in drug discovery for treatments,” he said.