Eli Lilly's experimental weight loss drug retatrutide produced up to 28 percent weight loss in a phase 3 clinical trial, with some participants losing as much as 85 pounds. The results, from the TRIUMPH-1 trial, represent the greatest weight loss ever recorded in a medication study.
According to Healthline, retatrutide is a triple hormone receptor agonist administered once weekly by injection. Unlike existing drugs such as Ozempic and Wegovy, which activate only the GLP-1 receptor, retatrutide activates three receptors: glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon.
In the trial, participants received one of three doses: 4 mg, 9 mg, or 12 mg. After 80 weeks, those on the 4 mg dose lost an average of 19 percent of their body weight, or about 47 pounds. Participants on the 9 mg dose lost an average of 25.9 percent, about 64 pounds. Those on the highest dose, 12 mg, lost an average of 28.3 percent, roughly 70 pounds. Participants who received a placebo lost an average of 2.2 percent, or about 5.5 pounds.
At 104 weeks, participants with a baseline body mass index of at least 35 achieved an average weight loss of 30.3 percent, equal to approximately 85 pounds.
Lilly stated in a press release that at 80 weeks, all doses of retatrutide "met the primary and key secondary endpoints for obesity, delivering clinically meaningful weight loss."
"TRIUMPH-1 highlights the importance of options and the potential for retatrutide to help people across various stages of their obesity journey," said Kenneth Custer, PhD, executive vice president and president of Lilly Cardiometabolic Health, in the same press release. "Together with Zepbound and Foundayo, retatrutide could build on Lilly's commitment to match treatments to the needs and preferences of patients."
Mir Ali, MD, a bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, California, who was not involved in the trial, reviewed the results. "These results indicate that retatrutide is a promising new drug that appears more effective than currently available medications," Ali said.
The trial's lead investigator, Ania Jastreboff, MD, a professor of medicine and pediatrics, also commented on the findings. "It was impressive to see that every dose of retatrutide resulted in clinically meaningful weight reduction for nearly all participants, and people with severe obesity on the highest dose lost on average 30% of their body weight over two years," Jastreboff said.
Beyond weight loss, retatrutide produced improvements in several cardiovascular risk factors, including waist circumference, cholesterol levels, and blood pressure. Lilly has not yet announced a timeline for seeking regulatory approval, but the phase 3 results position retatrutide as a potential next step in obesity treatment options.
