Two Phase III clinical trials led by Northwestern University have shown that a new experimental injectable weight-loss drug, Retatrutide, reduces knee osteoarthritis pain in overweight patients.
The trials, which involved more than 1,000 participants in total, found that two-thirds of those receiving the highest dose of the drug experienced at least a 50% reduction in knee pain, compared with 38% in the placebo group. At the same time, patients lost approximately 25% of their body weight. The findings were published in the scientific journal The New England Journal of Medicine.
Unlike currently available GLP-1 drugs (semaglutide and tirzepatide), which target one or two receptors and lead to 10–20% weight loss, Retatrutide, developed by pharmaceutical company Eli Lilly, activates receptors for three different naturally occurring hormones. In addition to reducing pain and promoting weight loss, the once-weekly injection lowers blood pressure, lipid levels and systemic inflammation.
According to Thomas Schnitzer, a professor at Northwestern University, the main factor behind pain reduction is the decreased mechanical stress on the knees resulting from weight loss. Nevertheless, diet and physical activity remain the cornerstone of osteoarthritis management, as GLP-1 drugs are associated with muscle loss, while muscle strength is critically important for stabilizing the knee joint.
Patients requiring total knee replacement surgery were excluded from the clinical trials. The main unanswered question for researchers is whether Retatrutide can slow osteoarthritis progression sufficiently to help patients avoid surgery in the future. Further research is also needed to understand the drug’s anti-inflammatory mechanism and assess its effectiveness in people with normal body weight, as the trials included only overweight and obese participants.
