Retatrutide Cut Knee Pain by Half in 63% to 70% of Patients

By Grace Kim

Retatrutide cut knee pain by at least half for 63% to 70% of adults with obesity and painful knee osteoarthritis who received either of two higher doses in phase 3 testing.

Northwestern University reported the results on Monday from two critical phase 3 trials, TRIUMPH-4 and TRIUMPH-1-OA. The New England Journal of Medicine, a peer-reviewed journal, published the findings, which showed an average 24% weight loss among patients taking the highest dose.

How much weight did patients lose?

Northwestern reported three core results from the two trials, with 1,019 participants in total:

• Participants on the highest dose lost an average of 24% of their body weight, and some lost more than 100 pounds.
• The placebo group lost less than 5%.
• Participants received retatrutide or placebo weekly for 68 to 80 weeks, and about 80% had a body-mass index above 35.

In plain terms, retatrutide delivered a much larger average weight loss than placebo.

How much did pain and function improve?

Northwestern said about 63% to 70% of participants who received either higher dose cut knee pain by at least 50%. Those participants also reported improved physical function.

Northwestern also said 38% of the placebo group reported halving pain. The placebo result tempers the treatment percentages but leaves a difference between the drug and control groups.

Eli Lilly developed retatrutide as a once-weekly injectable and funded both trials, Northwestern said. The report framed reduced knee pain as an unexpected benefit beyond weight loss.

The 38% placebo figure is essential context for the 63% to 70% treatment result.

How many people have painful knee osteoarthritis?

A Northwestern release put the number at about 15 million Americans. The university said the condition can make walking, climbing stairs or getting up from a chair difficult.

Current treatments, including physical therapy, pain relievers and steroid injections, often offer only short-term relief, Northwestern said. The university also said overweight or obesity can put extra stress on the knee joint and worsen pain.

Losing more than 10% of body weight through diet and exercise alone can be hard, particularly when pain already limits movement, Northwestern said. Against that constraint, the trial's 24% average loss cleared the 10% mark.

The trial addresses a pain problem that Northwestern estimates affects about 15 million Americans.

How does retatrutide compare with semaglutide and tirzepatide?

Northwestern's report compared retatrutide with popular GLP-1 drugs such as semaglutide and tirzepatide. It said those drugs target one or two hormone receptors and typically deliver 10% to 20% weight loss.

Retatrutide activates receptors for three naturally occurring hormones. In the two trials, Northwestern said, that translated into 20% to 25% weight loss.

On the report's numbers, retatrutide posted the stronger average result. Eli Lilly funded both studies, and Northwestern did not present a head-to-head trial of the three drugs.

Retatrutide landed at the top of the report's weight-loss range, but the comparison remained indirect.

What remains unanswered?

Northwestern's announcement left the broader case open. It did not name the issue behind its claim that the biggest question remained unanswered, and it did not report whether pain relief persisted after the 68-to-80-week treatment periods.

The trial population also limits the conclusion. All 1,019 participants had obesity, and about 80% had a BMI above 35. The results do not show how retatrutide would perform among people with painful knee osteoarthritis who do not have obesity.

For Eli Lilly, the next evidence must show whether the pain benefit lasts and whether the experimental drug can become more than a weight-management drug. Until then, the 63% to 70% reduction remains a striking phase 3 signal, not a settled standard for osteoarthritis care.