Eli Lilly and Company (NYSE: LLY) today announced that its experimental obesity therapy, retatrutide, demonstrated unprecedented efficacy in the Phase 3 TRIUMPH-4 trial, achieving an average weight loss of 28.7% among participants who completed 68 weeks of treatment. The results could signal a new standard in metabolic and obesity care, though the study also noted higher discontinuation rates compared with existing therapies.

Retatrutide is a first-in-class triple hormone receptor agonist, simultaneously targeting GLP-1, GIP, and glucagon receptors. This approach builds on the dual-agonist mechanism of Lilly’s marketed therapy, tirzepatide.

The TRIUMPH-4 trial enrolled 445 adults with obesity or overweight, comparing once-weekly 9 mg and 12 mg doses of retatrutide against placebo. Participants receiving the 12 mg dose lost an average of 32 kg (71 lbs), while the 9 mg dose led to an average loss of 29 kg (64 lbs). Including participants who discontinued early, the 12 mg group still achieved nearly 24% weight loss after 68 weeks.

The trial also assessed patients with knee osteoarthritis, revealing significant improvements in pain and physical function. Participants reported reductions of up to 4.5 points on the WOMAC pain score, representing a 75.8% improvement, and over 12% of treated patients were entirely free of knee pain by the study’s conclusion.

“People with obesity and knee osteoarthritis often live with pain and restricted mobility and may eventually require total joint replacement,” said Dr. Kenneth Custer, Executive Vice President and President of Lilly Cardiometabolic Health. “We are encouraged by the TRIUMPH-4 results, which highlight the powerful impact of retatrutide on body weight, pain, and physical function.”

While the therapy’s efficacy exceeded expectations, the trial identified side-effect considerations. About 18% of patients on the 12 mg dose and 12% on the 9 mg dose discontinued treatment due to side effects, compared with 4% on placebo. Mild tingling or uncomfortable skin sensations occurred in roughly 20% of patients on the 12 mg dose, though this rarely led to discontinuation.