Eli Lilly (NYSE:LLY) climbed 3% in premarket trading Thursday after unveiling landmark Phase 3 data for its experimental triple-agonist therapy, retatrutide, showing extraordinary levels of weight reduction alongside major improvements in osteoarthritis symptoms.
In the TRIUMPH-4 study, individuals with obesity and knee osteoarthritis who received the highest 12 mg dose lost an average of 28.7% of their body weight — roughly 71.2 pounds — over a 68-week treatment period. The drug also produced a substantial reduction in WOMAC pain scores of up to 75.8% and delivered significant gains in physical functioning.
Both the 9 mg and 12 mg doses achieved all primary and key secondary endpoints. Nearly 40% of patients on the top dose shed at least 30% of their body weight, while almost 24% reached or exceeded a 35% reduction.
Retatrutide’s benefits extended beyond weight loss and joint-pain relief. The therapy improved several cardiovascular indicators, including lowering systolic blood pressure by 14.0 mmHg at the 12 mg dose. A post-hoc analysis also showed that 12–14% of treated patients reported being completely free of knee pain by the end of the study, compared to only 4.2% of those on placebo.
“People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement,” said Kenneth Custer, Ph.D., executive vice president and president, Lilly Cardiometabolic Health. “We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function.”
Common side effects reported in the trial included nausea, diarrhea, constipation, vomiting, and reduced appetite. Dysesthesia occurred in 8.8% of patients on the 9 mg dose and 20.9% on the 12 mg dose, but these cases were typically mild.
Lilly noted that seven additional Phase 3 studies investigating retatrutide in obesity and type 2 diabetes are on track to conclude in 2026.