Knee osteoarthritis pain relief – and massive weight loss – from new GLP-1

Two Phase 3 clinical trials that involved more than 1,000 adults have significantly strengthened the case for Eli Lilly's experimental GLP-1-based drug retatrutide to gain FDA approval for both weight loss and relief from knee osteoarthritis (OA).In two Northwestern University-led phase 3 trials, people prescribed high doses of retatrutide lost, on average, up to 25% of their body weight and across both studies, around two-thirds receiving the active injectable also reported at least a 50% reduction in knee OA pain.That said, those receiving the placebo self-reported a 38% reduction in OA pain.Retatrutide is a next-generation triple-hormone receptor agonist drug that's so far only approved by the US Food and Drug Administration (FDA) for what equates to "compassionate use." That use, however, was reportedly granted to just one American. However, the results of these two trials form a good case for the drug to be the next weight-loss GLP-1 on the US market.Like with other obesity medications before it, the drug had secondary positives that included reduced blood pressure and inflammation. “The findings are really saying for people who are overweight and have OA, if you lose a significant amount of weight with this treatment, there is a good chance that you’re going to get a meaningful reduction in your knee pain,” says corresponding author Dr. Thomas Schnitzer from Northwestern University's Feinberg School of Medicine. “A major factor is that you’re loading your knees less and therefore, there’s less pain and it allows you to increase your function.”Of course, weight loss itself helps relieve knee OA, but unlike single- or dual-receptor drugs like semaglutide or tirzepatide, a once-weekly injection of retatrutide activates three natural hormone receptors. This resulted in a higher percentage of weight loss.“Participants had remarkable responses,” notes Schnitzer. “Many of the people in this study lost considerable amounts of weight, with a few losing up to a hundred pounds or more.”The scientists concede that some questions remain, including whether those who aren't overweight can benefit from the pain relief aspect when it comes to knee OA.“These drugs are believed to have significant anti-inflammatory activity, but the mechanism is not entirely known,” Schnitzer adds. “Whether cutting down inflammation in the joint is also important in addition to reducing load needs more research, so this is still a first step, in my view. I’ve been working in the OA field for a long time, and I think this opens up opportunities to do a lot more studies to understand the condition better.”It's also worth noting that study co-authors are scientists who also work for Eli Lilly. However, this is not unusual in the age of companies leading the way with metabolic drug development such as Novo Nordisk.The research from both trials were published in the New England Journal of Medicine.Source: Northwestern University