Experimental weight-loss drug halves chronic knee pain in many patients, trials find

An experimental weight-loss drug significantly reduced chronic knee pain and improved mobility in people with obesity and knee osteoarthritis, according to two clinical trials led by researchers at Northwestern University in the United States. The results of the trials, funded by Eli Lilly, were published in The New England Journal of Medicine.

The trials evaluated retatrutide, a once-weekly injectable medication developed by Eli Lilly and Co. The drug, which is not yet approved by the US Food and Drug Administration (FDA), mimics three hormones involved in appetite and metabolism — GLP-1, GIP and glucagon — and has produced substantial weight loss in clinical trials.

The late-stage trials enrolled more than 1,000 adults who were overweight or obese, did not have diabetes, and experienced painful knee osteoarthritis. Participants were followed for 68 weeks in one trial and 80 weeks in the other.

Participants receiving the highest dose of retatrutide lost about a quarter of their body weight on average. A pooled analysis found that roughly two-thirds of those treated with the drug achieved at least a 50 percent drop in knee pain, compared with 38 percent of those receiving a placebo.

Painful knee osteoarthritis affects an estimated 15 million Americans, according to the researchers. Beyond pain relief and functional gains, participants experienced reductions in blood pressure, lower blood lipid levels and decreased systemic inflammation.

Dr Thomas J. Schnitzer, a professor at Northwestern University Feinberg School of Medicine and lead author of the study, said that for people who are obese, not diabetic, have radiographically confirmed knee osteoarthritis that has not progressed to bone on bone, and have consistent moderate knee pain, retatrutide treatment has the potential to result in a significant and meaningful reduction in knee pain and improvement in physical function, while providing cardiometabolic benefit.

Schnitzer said that while researchers anticipated benefits from the weight reduction, the complete relief of knee pain in one of every eight patients taking the drug was a surprise. For people with knee osteoarthritis, routine activities such as standing, walking and climbing stairs often become painful challenges.

Gastrointestinal problems were the most common side effects, and serious adverse events were more common among participants receiving retatrutide than among those receiving a placebo, the researchers said.

Conventional treatments — physical therapy, anti-inflammatory medications and steroid injections — often offer only limited or temporary relief, according to the researchers. Earlier research has found that losing 5 to 10 percent of body weight through diet and exercise can ease knee osteoarthritis symptoms, but losing more than 10 percent through those measures alone can be difficult, particularly when knee pain limits exercise, Schnitzer said.

Schnitzer stressed that the study had limitations. People with knee osteoarthritis who were not overweight or obese were not studied, and individuals who were obese and had more advanced osteoarthritis were also excluded, so there is no information on them. The trials also excluded patients who needed knee replacement surgery. Whether retatrutide slows osteoarthritis progression or reduces the need for future joint replacements remains unknown.

For individuals experiencing joint pain who may meet the study criteria, Schnitzer recommended discussing options with a healthcare provider. At the same time, he emphasized that medication should not replace healthy daily habits.