The company said retatrutide also reduces knee pain in patients
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Eli Lillys experimental weight-loss drug retatrutide led to an average weight reduction of up to 28.7%more than 71 poundsin adults with obesity or overweight and knee osteoarthritis.
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Participants also saw major reductions in knee pain, with scores on a standard osteoarthritis pain index improving by as much as 76%.
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The trial suggests retatrutide may help delay or avoid joint replacement in people with severe obesity and chronic knee pain, though side effects were common.
Ozempic and Wegovy may soon have new competition. A new Phase 3 clinical trial from Eli Lilly and Company suggests that its investigational drug retatrutide, described as a first-in-class triple agonist, may offer significant weight loss and pain relief for people struggling with both obesity and knee osteoarthritis.
Lilly released topline results from its TRIUMPH-4 study, which tested the two highest doses of retatrutide (9 mg and 12 mg) in adults without diabetes. Most participants 84% entered the trial with a BMI of 35 or higher, a level associated with elevated health risks and worsened joint deterioration. Retatrutide is being developed as a once-weekly injection, similar to other peptide weight-loss drugs.
The trial's findings were impressive: both doses achieved all primary and key secondary endpoints at 68 weeks, including large reductions in body weight, knee pain, and physical function scores.
Up to 28.7% weight loss and pain reduction
Participants taking retatrutide lost an average of 26.4% to 28.7% of their body weight, compared to just 2% for those on placebo. For the average enrollee, this translated to a weight loss of 64 to 71 pounds.
The company said pain relief was also dramatic. Using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), researchers reported pain score reductions of 74% to 76% with retatrutide, versus 40% with placebo. Improvements in physical function mirrored these results.
Some participants achieved exceptionally high levels of weight loss:
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25% or more weight loss: 4859% of retatrutide users
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30% or more weight loss: 3139%
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35% or more weight loss: 1824%
In a follow-up analysis, up to 14% of patients on retatrutide reported being completely free of knee pain after 68 weeks, compared with just 4% of those on placebo.
Beyond weight and pain
Researchers also observed improvements in several markers associated with cardiovascular risk, including non-HDL cholesterol, triglycerides, high-sensitivity C-reactive protein, and systolic blood pressure. At the highest dose, systolic blood pressure dropped by 14 mmHga meaningful reduction.
Lilly says these combined effects could make retatrutide an important future option for people needing substantial weight loss, especially when obesity aggravates conditions like osteoarthritis.
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 of Lilly Cardiometabolic Health. He noted the drugs powerful effect on both weight and joint symptoms.
Next steps
Full TRIUMPH-4 data will be presented at an upcoming medical meeting and published in a peer-reviewed journal. Lilly expects seven more Phase 3 trial readouts in 2026, including studies testing maintenance dosing.
Retatrutide remains investigational and is not yet approved by the FDA or any global regulator. Still, the results add to growing momentum behind next-generation weight-loss drugs that target multiple metabolic pathways.
Posted: 2025-12-11 14:37:15















