An experimental weight-loss medication reduced chronic knee pain and improved mobility in people with obesity and knee osteoarthritis, according to two clinical trials led by Northwestern University researchers.
The studies, funded by Eli Lilly and published in The New England Journal of Medicine, tested retatrutide, a once-weekly injection made by the drugmaker. The medication is not yet approved by the FDA. It acts on three hormones involved in appetite and metabolism: GLP-1, GIP and glucagon.
More than 1,000 adults took part. They were overweight or had obesity, did not have diabetes, and had painful knee osteoarthritis. After 68 or 80 weeks, participants receiving the highest dose had lost about a quarter of their body weight on average.
In a combined analysis, about two-thirds of people taking retatrutide saw their knee pain fall by at least half. That compared with 38% of participants given a placebo. Researchers also reported improvements in physical function, blood pressure and blood lipid levels, as well as reduced systemic inflammation.
Gastrointestinal issues were the most frequent side effects. Serious adverse events occurred more often among participants taking retatrutide than among those receiving placebo.
Thomas J. Schnitzer, a Northwestern University Feinberg School of Medicine professor and the study’s lead author, said the findings suggest the drug could benefit a particular group: people with obesity who do not have diabetes, have confirmed knee osteoarthritis that has not reached the “bone-on-bone” stage, and experience ongoing moderate pain.
Researchers expected weight loss to help, Schnitzer said, but were surprised that one in eight participants taking the drug reported complete relief from knee pain.
Knee osteoarthritis affects an estimated 15 million Americans. Everyday tasks such as standing, walking and climbing stairs can become painful. Existing options include physical therapy, anti-inflammatory medication and steroid injections, which may provide limited or temporary relief.
Earlier research suggests losing 5% to 10% of body weight through diet and exercise can ease symptoms. Losing more than that through lifestyle changes alone can be difficult, Schnitzer noted, especially when pain makes exercise harder.
The results also have limits. People who were not overweight or had obesity were not included, nor were those with more advanced osteoarthritis. The trials also excluded people who needed knee replacement surgery. It remains unclear whether retatrutide can slow the disease or reduce the likelihood of needing a joint replacement.
Schnitzer advised people with joint pain who may fit the study profile to discuss treatment options with a healthcare provider, particularly if they have struggled to lose weight. He also stressed that medication should not take the place of healthy habits: diet, exercise and options such as physical therapy should be considered, and exercise remains important for preserving muscle even when someone is taking weight-loss medication.
