Retatrutide in two phase 3 trials: about 25% weight loss and less knee osteoarthritis pain
In two Northwestern-led phase 3 trials with over 1,000 participants, the experimental Eli Lilly injectable cut body weight and knee pain in people with obesity.
Two phase 3 clinical trials led by Northwestern University, with more than 1,000 participants combined, tested retatrutide, an experimental once-weekly weight-loss injectable from Eli Lilly. Participants had painful knee osteoarthritis (OA) and were overweight or had obesity, according to news.northwestern.edu. Those taking the highest dose lost about one-quarter of their body weight on average northwestern.edu
news.northwestern.edunews.northwestern.eduOpen source ↗. The results will be published on Nov. 8 in the New England Journal of Medicine.
Weight and pain results
A pooled analysis of the two studies found that about two-thirds of participants receiving retatrutide had at least a 50% reduction in knee pain, compared with 38% of those receiving placebo. Pain was assessed with the WOMAC Pain index, on which participants rated pain from 0 to 10 at each visit. They also logged daily pain ratings in an app. Participants also had lower blood pressure, lower lipid levels and less systemic inflammation.
Retatrutide activates receptors for three distinct natural hormones. Currently available GLP-1 drugs such as semaglutide or tirzepatide target one or two receptors and typically result in 10%-20% weight loss. In this study, retatrutide produced 20%-25%. Some participants lost up to a hundred pounds or more, said corresponding author Dr. Thomas Schnitzer of Northwestern University Feinberg School of Medicine. He linked the pain relief mainly to lower load on the knees.
Open questions
The trials are called TRIUMPH-4 and TRIUMPH-1-OA. Philip Conaghan of the University of Leeds will present TRIUMPH-4 on Nov. 8 at the American College of Rheumatology annual meeting in Orlando, Florida. The second study will be shown the same day in a poster session northwestern.edu
news.northwestern.edunews.northwestern.eduOpen source ↗.
People who needed a knee replacement were excluded, so it is unknown whether retatrutide slows OA progression enough to reduce the need for joint replacement. People who are not overweight were also not included, so the effect in them is unknown.
The drugs are believed to have significant anti-inflammatory activity, but the mechanism is not entirely known, Schnitzer said. Whether reduced joint inflammation matters in addition to reduced load needs more research. He described the work as a first step. Schnitzer said the drug could be an option if it is approved by the U.S. Food and Drug Administration. The study was funded by Eli Lilly, and Lilly scientists are among the co-authors.
