Experimental drug could offer more weight loss than any drug now on the market, study finds

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 Diabetes Association’s annual meeting in San Diego. The findings were simultaneously published in The New England Journal of Medicine.

If the results are confirmed in a larger, phase 3 clinical trial — which is expected to run until late 2025 — retatrutide could leapfrog 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; FDA approval of the drug for weight loss is expected this year or early next year.

The new findings, according to Dr. Shauna Levy, a specialist in obesity medicine and the medical director of the Tulane Bariatric Center in New Orleans, are “mind-blowing.”

Levy, who was not involved with the research, said the drug seems to be delivering results that are approaching the effectiveness of bariatric surgery. “It’s certainly knocking on the door or getting close,” she said. 

The new study underscores the rapid upswing in recent years in the discovery of new treatments for weight loss as companies invest in a new class of medicines called GLP-1 agonists, which mimic a hormone that helps reduce food intake and appetite. 

The drugs have been “transformative to say the least,” Levy said. “They’ve given so many people hope that felt sort of helpless in this fight against the disease of obesity.”

Semaglutide, the active ingredient in the highly popular Novo Nordisk 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, plus one other hormone: glucagon. GIP is thought to improve how the body breaks down sugar; glucagon may reduce appetite and help metabolism run more efficiently. 

“This can explain why retatrutide yields more effective weight loss,” said Dr. Holly Lofton, the director of the weight management program at NYU Langone Health. She was not involved with the trial, although she has previously served on an advisory board for Ozempic and Wegovy-maker Novo Nordisk.

Dr. Dan Skovronsky, Eli Lilly’s chief scientific and medical officer, told NBC News that retatrutide is attempting to harness 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 we’ve turned them into medicines,” Skovronsky said. 

How does retatrutide compare to other weight-loss drugs?

Lilly’s phase 2 trial looked at 338 adults who were obese or overweight and were randomized to receive a placebo or one of four dosages of retatrutide. The drug was given as a weekly injection.

Participants had a body mass index, or BMI, of 27 or greater. The results published Monday did not include patients with Type 2 diabetes, a group that is also prescribed GLP-1 medications because of their effects on blood sugar levels. A separate trial is looking at retatrutide for patients with Type 2 diabetes.

After 24 weeks, patients taking the highest dose — 12 milligrams — lost, on average, 17.5% of their body weight, the equivalent of, on average, 41 pounds, according to the company. By 48 weeks, the weight loss increased to 24.2% of their body, or 57.8 pounds.

“The degree of efficacy, it was definitely striking,” said Dr. Ania Jastreboff, an obesity medicine physician scientist at Yale University School of Medicine and the lead author on the phase 2 study. 

What’s more, at the end of 48 weeks the weight loss had not yet plateaued, meaning they could have potentially lost even more weight had they stayed on the medication for a longer period of time, she said.

Jucynthia Jessie, 44, of Laplace, Louisiana, participated in the trial and lost 60 pounds.

“I was totally surprised,” Jessie said. “You don’t know if you have the placebo or not, so once I started seeing the results — no one ever told me anything different — but I saw the results for myself and so I was really surprised.” (Jessie wasn’t told that the trial was studying retatrutide — only that it was a study on a weight loss drug — but the research facility confirmed with NBC News.)

She’s gained back about 15 pounds in the nine months since she completed the trial, but said she still thinks the weight loss is sustainable with healthy lifestyle choices.

Weight loss in the trial seemed to happen quicker than other weight loss medications, according to Jastreboff. Novo Nordisk’s semaglutide was found to reduce body weight, on average, by around 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% on average, or about 52 pounds, after 72 weeks. To be sure, these are not direct comparisons because the drugs were not compared in a head-to-head clinical trial.

Dr. Fatima Cody Stanford, a physician specializing in obesity at Massachusetts General Hospital in Boston, said that when patients lose weight very quickly — more than 10 pounds a month — they can be at risk for developing gallstones. It’s a known side effect following bariatric surgery, she said, and would be something she would keep an eye on. In clinical trials, tirzepatide and semaglutide have also been associated with a small but slightly increased risk of gallbladder disease, including gallstones.

The speed of the weight loss seen with retatrutide was not a concern to Lofton. Rapid weight loss is usually only detrimental “if it is achieved in an overly restrictive manner, such as drinking only water or eating only cabbage,” she said.

Still, she said she wanted to see more data on how much lean body mass — that is, weight in the body that isn’t fat, including bone muscle and organs — 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 other weight loss medications, Skovronky said. Side effects from Ozempic and Wegovy, for example, include nausea, vomiting, diarrhea and constipation. Generally, people experience those side effects as they ramp up the dosage at the start of treatment, but the side effects usually go away after prolonged use. 

Who would retatrutide be for? 

While FDA approval of Lilly’s other weight loss drug, tirzepatide, is expected in the coming months, Skovronksy said he believes that it can coexist with retatrutide. 

“We don’t stop with one medicine for Alzheimer’s disease,” he said. “The same will be true for metabolic disease, including obesity and Type 2 diabetes. We’ll need different kinds of medicines for different patients.”

Jastreboff agreed. Retatrutide could be an option for people who don’t respond well to other weight loss medications. Given its potency, it could also be useful for people who need to lose a substantial amount of weight, she said. 

Still, retatrutide has a long way to go before it’s available to the public. 

“It is early days,” Skovronsky said. The company has started enrolling participants in a larger phase 3 clinical trial, which will include thousands of participants. The trial is expected to be completed in December 2025, according to clinicaltrials.gov. After that, if the results hold up, the drug would need to go through the FDA’s rigorous review process. 

Skovronsky said he hopes that retatrutide could one day provide the same levels of weight loss seen with bariatric surgery.

He also said that retatrutide and drugs like it could potentially be used to treat obstructive sleep apnea as well as decrease the risk of heart disease. 

“This is really a golden age of drug discovery for treatments,” he said.

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