Obesity Patients Lost Nearly 30 percent of Their Body Weight on a New Experimental Drug and Many Saw Their Knee Pain Disappear

An experimental drug links dramatic weight loss with relief from arthritis pain.

In a new clinical trial, people with obesity and knee osteoarthritis who took an experimental drug from Eli Lilly lost large amounts of weight—nearly a third of their body weight in just over a year. Along with the weight loss came something many participants had not expected: less knee pain, and in some cases, none at all.

In this case, one treatment could ease two conditions that often reinforce each other. Extra weight strains the knee joint. Knee pain limits movement, making weight loss harder. Retatrutide, the experimental drug in question, appears to loosen that vicious circle.

The findings come from a Phase 3 trial called TRIUMPH-4, part of a broader effort to push obesity drugs into new territory.

Substantial Weight Loss

The TRIUMPH-4 study followed 445 adults with obesity or overweight and confirmed knee osteoarthritis for 68 weeks. Most participants (84%) had a body mass index of at least 35, which corresponds to severe obesity. They were randomly assigned to receive a placebo or one of two once-weekly doses of retatrutide, 9 milligrams or 12 milligrams.

By the end of the study, the differences were stark. Participants taking the highest dose lost an average of 28.7% of their body weight (about 71 pounds). Those on the lower dose lost 26.4%. The placebo group lost just over 2%, according to Eli Lilly’s announcement.

More than half of the participants on the highest dose lost at least a quarter of their starting weight. Nearly one in four lost at least 35%. The results exceed what has been seen with current blockbuster obesity drugs like Ozempic, pushing medical weight loss closer to the range typically associated with bariatric surgery. The trial also showed improvements in blood pressure, cholesterol, and markers of inflammation.

Knee Relief

Weight loss alone can ease pressure on arthritic joints. But the magnitude of pain relief in TRIUMPH-4 stood out.

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Participants rated knee pain using the WOMAC scale, which runs from zero to 10. Those taking 12 milligrams of retatrutide reported an average pain reduction of 4.4 points, or about a 74% drop. Physical function scores improved by a similar amount. In a post-hoc analysis, roughly one in eight participants reported being completely free of knee pain at the end of the trial.

“People with obesity and knee osteoarthritis often live with pain and restricted mobility, and may eventually require total joint replacement,” said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health. “We are encouraged by the results of TRIUMPH-4.”

Orthopedic specialists reacted with guarded enthusiasm. Dr. MaCalus Hogan, chair of orthopedic surgery at the University of Pittsburgh Medical Center, called the findings “a huge step forward in weight loss management and relief of orthopedic pain,” as per The New York Times.

Others stressed limits. “We need to have data on whether these drugs have the same impressive reduction in knee pain in the majority of knee osteoarthritis patients who are not this obese,” Dr. David Felson, a rheumatologist at Boston University Medical Center, also told The New York Times.

Lilly has said the study was not designed to determine whether pain relief exceeded what would be expected from weight loss alone.

Power, side effects, and what comes next

Retatrutide belongs to a fast-moving class of drugs that target hormones involved in appetite and metabolism. Unlike existing treatments, it activates three receptors at once: GLP-1, GIP, and glucagon. Why this combination produces such dramatic effects remains unclear.

The weight loss power comes with tradeoffs. Gastrointestinal side effects were common. Many participants reported nausea, diarrhea, constipation, or vomiting. About 18% of people on the highest dose stopped treatment because of adverse events, compared with roughly 5% in the placebo group. Some discontinued because of what the company described as “perceived excessive weight loss.”

These numbers highlight a central reality of obesity medicine. Even highly effective drugs will not suit everyone. Some people will not tolerate the side effects. Others may not want or need such large changes in weight.

Lilly expects results from seven additional Phase 3 trials of retatrutide by 2026, testing the drug in diabetes, sleep apnea, cardiovascular disease, and other obesity-related conditions.

For people living with knee osteoarthritis, the implications are immediate. Weight loss has long been one of the most effective ways to reduce pain, but also one of the hardest to sustain. A drug that reliably delivers large losses could reshape how doctors treat joint disease.

Retatrutide remains experimental. Its long-term safety, cost, and role in care are still unknown. But TRIUMPH-4 suggests that the ceiling for obesity treatment is still rising—and that, for some patients, the payoff may be felt not just on the scale, but with every step.