People lost up to 85 pounds on Lilly’s experimental weight loss drug, company says

Eli Lilly’s highly anticipated new weight loss drug, retatrutide, helped people lose up to 30% of their body weight, about 85 pounds, in a late-stage clinical trial, the drugmaker said in a news release Thursday. The results are on par with bariatric surgery, which helps people lose on average 25% to 35% of their total body weight within one to two years. “This is the largest weight loss I’ve ever seen in any medication trial,” said Dr. Susan Spratt, an endocrinologist and the senior medical director for the Population Health Management Office at Duke Health in North Carolina. She was not involved in the trial. “This is huge.” Lilly has not yet filed for Food and Drug Administration approval for retatrutide. It has said it expects to file for approval as early as this year. Retatrutide is in the same class of medications as Wegovy and Zepbound, which mimic a hormone called GLP-1. Retatrutide, however, is a so-called triple agonist — in addition to GLP-1, it also mimics the hormones GIP and glucagon. (Lilly’s Zepbound, a double agonist, mimics GLP-1 and GIP.) “We’ve already seen a tremendous impact from semaglutide and tirzepatide — the GLP-1 and the GLP-1 and GIP,” Spratt said. “To see a drug that could possibly do even more weight loss is an even bigger game changer.” Dr. Shauna Levy, medical director of the Tulane Weight Loss Center, said the current GLP-1s may not provide enough weight loss for people with severe obesity, classified as a body mass index of at least 35. “Bariatric surgery can provide that, but it seems like retatrutide is also going to be an effective tool to help patients with a higher BMI achieve a healthy weight,” Levy said. Lilly’s results are based on a phase 3 trial of about 2,300 patients with obesity or who are overweight. The drug company did not publish the full results in a medical journal. Participants taking the highest weekly dose of retatrutide lost, on average, 28% of their body weight, about 70 pounds, with nearly half losing 30% or more. The trial ran for 80 weeks. A smaller group of patients with severe obesity continued to take the drug for up to 104 weeks and lost an average of 85 pounds. By comparison, in trials, patients taking the highest dose of Zepbound lost around 21% of their body weight over 72 weeks and patients taking the highest dose of Wegovy lost around 15% after 68 weeks. (Those are not direct comparisons, as the drug were not evaluated in head-to-head clinical trials.) Nausea, constipation and diarrhea were among the side effects of retatrutide — they are often seen with GLP-1 drugs. Lilly also said that compared with placebo, patients taking retatrutide also had more reports of unusual or uncomfortable skin sensations and urinary tract infections. The rate of people dropping out of the trial was higher than what was seen for Zepbound but similar to rates seen with Wegovy, Lilly said. Retatrutide is among the next generation of weight loss drugs expected to come to the market, which aim to provide greater weight loss, fewer side effects or more convenience. If it is approved, Spratt said, retatrutide could be ideal for patients who do not lose weight on the current generation of GLP-1s — an issue, she said, that is likely to be more common than thought. “There’s about 10% of patients that don’t respond to GLP-1s,” Spratt said. “This could be very useful for patients who are GLP-1 non-responders.”