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.
The trials, which were funded by Eli Lilly and published in The New England Journal of Medicine, evaluated retatrutide, a once-weekly injectable medication developed by Eli Lilly and Co.
Retatrutide, which is not yet FDA-approved, mimics three hormones involved in appetite and metabolism — GLP-1, GIP and glucagon — and has produced substantial weight loss in clinical trials.
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The late-stage trials enrolled more than 1,000 adults who were overweight or obese, did not have diabetes, and experienced painful knee osteoarthritis.
After 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% drop in knee pain, compared with 38% of those receiving a placebo.
Beyond pain relief and functional gains, participants experienced reductions in blood pressure, lower blood lipid levels and decreased systemic inflammation, according to the researchers.
Gastrointestinal problems were the most common side effects, and serious adverse events were more common among participants receiving retatrutide than among those receiving placebo.
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Dr. Thomas J. Schnitzer, a professor at Northwestern University Feinberg School of Medicine and lead author of the study, said the findings offer therapeutic potential for specific groups of patients.
“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 their knee pain and improvement in their physical function while providing cardiometabolic benefit,” Schnitzer told Fox News Digital.
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, Schnitzer said.
Painful knee osteoarthritis affects an estimated 15 million Americans, often turning routine activities such as standing, walking and climbing stairs into painful challenges.
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Conventional treatments include physical therapy, anti-inflammatory medications and steroid injections, which often offer only limited or temporary relief, according to the researchers.
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While earlier research has found that losing 5% to 10% of body weight through diet and exercise can ease knee osteoarthritis symptoms, losing more than 10% through those measures alone can be difficult, particularly when knee pain limits exercise, Schnitzer said.
Despite the study’s promising outcomes, Schnitzer stressed that there were some limitations.
“People with knee OA who were not overweight or obese were not studied, and individuals who were obese and had more advanced OA were also excluded, so we have no information on them,” he said.
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The trials 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.
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“If someone fits the profile noted above, and they have been unsuccessful at losing weight, they should speak to their physician about the possibility of being treated with a medication that would help them lose weight, as that could also reduce their knee pain as well as provide cardiometabolic benefits,” Schnitzer said.
At the same time, he emphasized that medication should not replace healthy daily habits.
“Before starting pharmacologic treatment for knee pain, people who are overweight should try diet and exercise and consider interventions such as physical therapy,” Schnitzer advised.
“Also, even for people on weight-loss medications, exercise is an important part of any treatment plan to maintain as much muscle as possible.”
