Eli Lilly’s next-generation obesity treatment candidate, retatrutide, has met all primary endpoints in two additional global Phase 3 clinical trials. Based on these promising results, Lilly plans to submit a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) in the first quarter of next year.
Lilly announced the topline results of its global Phase 3 trials, TRIUMPH-2 and TRIUMPH-3, on Thursday.
Industry sources reported that Lilly has now secured positive results in a total of five Phase 3 trials, including these latest findings. The pharmaceutical giant aims to pursue global approval applications for obesity, knee osteoarthritis pain, and obstructive sleep apnea indications.
Retatrutide is the world’s first triple hormone receptor agonist, simultaneously activating glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and glucagon receptors.
Currently, Novo Nordisk’s Wegovy is a GLP-1 monotherapy, while Lilly’s Zepbound (tirzepatide) is a dual agonist for GIP and GLP-1. Retatrutide goes a step further by adding glucagon action, which helps suppress appetite, regulate blood sugar, and increase energy expenditure, potentially maximizing weight loss effects.
Both trials met their primary endpoints. TRIUMPH-2 focused on adults with obesity or overweight and type 2 diabetes. After 80 weeks of treatment, the average weight loss rates for the 4 mg, 9 mg, and 12 mg groups were 12.7%, 19.1%, and 20.8%, respectively.
The 12 mg group, which received the maximum dose, lost an average of 22.5 kg (about 49.6 lbs), while the placebo group only saw a 4.0% reduction. Hemoglobin A1c (HbA1c) also decreased by up to 1.6 percentage points, confirming both weight loss and blood sugar improvement effects.
TRIUMPH-3 included adults with severe obesity and existing cardiovascular disease, regardless of type 2 diabetes status. After 80 weeks, the average weight loss rates for the 9 mg and 12 mg groups were 21.6% and 22.6%, respectively. The maximum dose group lost an average of 25.3 kg (about 55.8 lbs), while the placebo group had a weight loss rate of 3.2%.
The trials also demonstrated improvements in cardiovascular risk factors. The 12 mg group saw triglycerides drop by 37.0%, non-HDL cholesterol decrease by 16.5%, and systolic blood pressure lower by an average of 9.3 mmHg. Waist circumference decreased by an average of 19.0 cm (about 7.5 inches), and high-sensitivity C-reactive protein (hsCRP) fell by 51.2%.
However, major adverse cardiovascular events (MACE) occurred less frequently than expected in both the retatrutide and placebo groups, with no statistically significant differences observed. The most common side effects included diarrhea, nausea, constipation, decreased appetite, and vomiting, most of which were mild to moderate.
Kenneth Custer, President of Lilly’s Diabetes and Metabolic Diseases division, stated that Retatrutide has demonstrated strong efficacy through five positive Phase 3 trials. This comprehensive data supports the global application not only for obesity but also for knee osteoarthritis pain and obstructive sleep apnea indications.
Lilly is currently finalizing the manufacturing and quality control (CMC) data required for the application and plans to submit the BLA to the FDA in the first quarter of 2027.