Eli Lilly and Company reported positive topline results from its Phase 3 TRIUMPH-1 clinical trial, showing that investigational obesity treatment retatrutide delivered substantial and clinically meaningful weight loss in adults with obesity or overweight and at least one weight-related condition, but without diabetes.
The results position retatrutide as a potential major contender in the fast-growing obesity treatment market, where pharmaceutical companies are racing to develop more effective therapies for chronic weight management and cardiometabolic disease.
Retatrutide is an investigational, first-in-class triple hormone receptor agonist targeting glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors. Lilly said the treatment met all primary and key secondary endpoints in the 80-week TRIUMPH-1 study across all tested doses—4 mg, 9 mg and 12 mg.
The trial enrolled adults living with obesity or overweight who also had at least one weight-related comorbidity but did not have diabetes. Participants receiving retatrutide experienced marked reductions in body weight compared with placebo, with higher doses producing stronger effects.
At the study’s primary endpoint at 80 weeks, participants treated with 9 mg and 12 mg doses lost an average of 64.4 pounds (25.9%) and 70.3 pounds (28.3%) of body weight, respectively. Those receiving the 4 mg dose lost an average of 47.2 pounds (19.0%). By comparison, placebo recipients experienced a 2.2% reduction in body weight.
Notably, Lilly said 65.3% of participants taking the 12 mg dose achieved a body mass index (BMI) below 30, moving out of the obesity category after 80 weeks of treatment. Among individuals who entered the study with severe obesity, defined as a BMI of 40 or higher, 37.5% crossed below the obesity threshold.
Further results from a pre-specified extension study involving participants with a BMI of 35 or greater suggested sustained benefits over a longer treatment period. Individuals continuing retatrutide 12 mg through 104 weeks achieved average weight reductions of 85 pounds, equivalent to 30.3% of body weight.
Beyond weight reduction, the therapy also demonstrated improvements in several cardiometabolic indicators. Lilly reported significant reductions in waist circumference, triglycerides, non-HDL cholesterol, systolic blood pressure and high-sensitivity C-reactive protein, a marker linked to inflammation and cardiovascular risk.
Ania Jastreboff, professor of medicine and pediatrics at the Yale School of Medicine and lead investigator for the trial, described the findings as notable because meaningful weight reduction occurred across all dose levels. She highlighted that patients with severe obesity receiving the highest dose lost approximately 30% of their body weight over two years, while also showing measurable cardiometabolic improvements.
Lilly executives said the findings reinforce the need for multiple treatment approaches tailored to the biological complexity of obesity. Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health, said retatrutide demonstrated flexibility across dose levels, ranging from nearly 20% weight loss at lower doses to reductions approaching levels traditionally associated with bariatric surgery at higher doses.
The safety profile observed in TRIUMPH-1 was generally consistent with other incretin-based therapies, Lilly said. The most commonly reported adverse events included nausea, diarrhea, constipation and vomiting, with incidence rates increasing at higher doses. Most side effects were mild to moderate, and discontinuation rates due to adverse events ranged from 4.1% to 11.3%, compared with 4.9% in the placebo group.
Additional TRIUMPH-1 findings are expected to be presented at the annual scientific sessions of the American Diabetes Association. Lilly said further results from the broader TRIUMPH Phase 3 program, including studies involving people with type 2 diabetes and cardiovascular disease, will be shared later this year.