Lilly's Retatrutide Cut Weight by 21 Percent in a Diabetes Trial. That Group Usually Loses Less on These Drugs.

Semaglutide and tirzepatide, the GLP-1 drugs sold as Ozempic, Wegovy, Mounjaro and Zepbound, are already approved for weight loss. People with type 2 diabetes typically lose less on them than people without diabetes do. A phase 3 trial published Tuesday in The Lancet found a third drug, Eli Lilly's retatrutide, may not follow that pattern. Participants with type 2 diabetes on the highest tested dose lost an average of 49.6 pounds, about 21 percent of body weight, over 80 weeks. Some patients lost as much as 60 pounds, Eli Lilly said, as reported by NBC News.

The study, called TRIUMPH-2, enrolled 1,152 adults with obesity or overweight and type 2 diabetes. Average starting weight was about 234 pounds, with an average BMI of 38. Volunteers took a weekly injection of 4, 9 or 12 milligrams of retatrutide, or a placebo, for 80 weeks. Those on placebo shed an average of 9.3 pounds. At 4 milligrams, the average drop was 29.8 pounds. At 9 milligrams, it reached 45.4 pounds.

What sets retatrutide apart

Retatrutide works differently from the GLP-1 drugs already on the market. Semaglutide targets one hormone receptor, GLP-1. Tirzepatide targets two, GLP-1 and GIP. Retatrutide adds a third, glucagon, making it what researchers call a triple agonist, the first of its kind to reach a phase 3 trial. "We achieved a new high-water mark for what's possible in terms of weight loss," said Daniel Skovronsky, Eli Lilly's chief scientific and product officer.

By the end of the study, roughly six in 10 participants on the highest dose no longer met the BMI threshold for obesity. Blood sugar control improved as well. A1C measures average blood sugar over the prior two to three months. It fell by up to 1.6 percentage points on retatrutide, versus 0.2 on placebo. Up to 40 percent of the group reached an A1C below 5.7 percent, the level that separates diabetes and prediabetes from a normal reading.

“It rivals gastric bypass surgery without the surgery.”

Spratt was not involved in the trial and does not receive funding from Eli Lilly. She said many diabetes medications, including insulin, tend to cause weight gain, which she called discouraging for patients trying to manage the disease well. In earlier trials, people with type 2 diabetes lost up to 10 percent of body weight on semaglutide, or 21 pounds. On tirzepatide, they lost up to 15 percent, or 34 pounds. Lilly did not test retatrutide directly against either rival, so the comparison is not head to head.

The caution alongside the enthusiasm

Not every doctor reads the data the same way. Dr. Michelle Ponder, an assistant professor of medicine at Duke University School of Medicine who was not involved in the trial, called the results very exciting. She also said retatrutide may be too strong for some patients, particularly those with mild diabetes or only slightly elevated weight. Those patients, she said, may be better suited to medications already on the market, such as Ozempic or Mounjaro.

Side effects in the trial matched other GLP-1 drugs: diarrhea, nausea, constipation and vomiting, which Lilly described as mild to moderate. About 8 percent of participants on the highest dose stopped taking retatrutide, compared with about 5 percent on placebo. Seven participants died during the trial; the Lancet paper attributed those deaths to causes unrelated to treatment. Randy Seeley, a University of Michigan professor, has worked as a paid Lilly consultant in the past but was not involved in TRIUMPH-2. He said rapid weight loss carries its own risks, including gallstones and micronutrient deficiencies. "If you're eating very few calories, it's harder and harder to get all of the other things you need from your food," he said.

A companion trial looked at people with obesity or overweight who did not have diabetes. Published the same day in the New England Journal of Medicine, it found retatrutide produced up to 25 percent weight loss over 80 weeks. A subset of those with severe obesity lost up to 30 percent of body weight after 104 weeks.

Lilly has not yet submitted retatrutide to the Food and Drug Administration. The company plans to file for approval in early 2027, Skovronsky said. Unauthorized compounded versions of the drug are already being sold through med spas and wellness platforms, often labeled for research use only. Lilly has filed lawsuits against sellers of those versions.