Eli Lilly has put out new detail on TRIUMPH-4, the phase 3 trial of retatrutide in people with obesity and knee osteoarthritis. In a release dated 5 November, the company says retatrutide lowered knee pain by up to an average of 4.5 points, or 75.8 percent, from a baseline of 6.0 on the WOMAC pain scale. It adds that more than 1 in 8 retatrutide-treated patients had no knee pain at the end of the trial.
The full results go to the American College of Rheumatology Convergence meeting in Orlando, in a plenary on Sunday 8 November. Retatrutide is a once-weekly injectable that acts on three hormone receptors at once: GIP, GLP-1 and glucagon. It is still investigational.
How the trial was run
TRIUMPH-4 was a randomised, double-blind, placebo-controlled study lasting 68 weeks. Lilly's December 2025 topline announcement says it enrolled 445 adults with obesity or overweight and knee osteoarthritis, without diabetes, split evenly between retatrutide 9 mg, retatrutide 12 mg and placebo. Everyone assigned to retatrutide started at 2 mg a week and stepped up every four weeks to the target dose.
Average baseline weight was 112.7 kg and average BMI was 40.4. The two co-primary endpoints were the change in body weight and the change in WOMAC knee pain score at week 68.
What Lilly reported
On the efficacy estimand, which counts people while they stayed on treatment, average weight loss was 26.4 percent on 9 mg and 28.7 percent on 12 mg, against 2.1 percent on placebo. The 12 mg figure is 32.3 kg, or 71.2 lb.
On pain, the WOMAC score fell by 4.5 points on 9 mg and 4.4 points on 12 mg, from a baseline of 6.0, against 2.4 points on placebo. Lilly says the percentage changes in pain and function were not pre-specified and come from post-hoc analysis. The share of patients completely free of knee pain at 68 weeks was 14.1 percent on 9 mg and 12.0 percent on 12 mg, against 4.2 percent on placebo, also a post-hoc figure based on observed data.
Side effects and dropouts
The most common adverse events were gastrointestinal. On 9 mg and 12 mg respectively, nausea affected 38.1 and 43.2 percent of patients, diarrhoea 34.7 and 33.1 percent, constipation 21.8 and 25.0 percent and vomiting 20.4 and 20.9 percent. On placebo the figures were 10.7, 13.4, 8.7 and 0 percent. Lilly says these match what is seen with other incretin drugs.
Dysesthesia, an abnormal skin sensation such as tingling or sensitivity, was reported by 8.8 percent on 9 mg and 20.9 percent on 12 mg, against 0.7 percent on placebo. Across all participants, 12.2 percent on 9 mg and 18.2 percent on 12 mg stopped treatment because of adverse events, against 4.0 percent on placebo. Among people with a baseline BMI of 35 or more, the rates were 8.8 percent, 12.1 percent and 4.8 percent.
What comes next
TRIUMPH-4 was the first TRIUMPH phase 3 trial to report, in December 2025. The wider programme covers obesity, sleep apnoea, chronic low back pain, cardiovascular and renal outcomes and fatty liver disease. Lilly's 5 November release states that retatrutide cannot be legally sold or marketed for human use.
OrientSciences has worked from Lilly's two releases. The full presentation on 8 November, and any peer-reviewed publication, will show trial detail that the company releases do not, such as the pain results across all groups and the safety data by dose.