New GLP-1 Drug Shows Promise for Knee Arthritis Pain Relief and Major Weight Loss

Results from two Phase 3 clinical trials involving more than 1,000 adults have bolstered the case for Eli Lilly's experimental GLP-1-based drug retatrutide to win FDA approval for both weight loss and relief from knee osteoarthritis (OA).

In two Northwestern University-led phase 3 studies, participants given higher doses of retatrutide lost as much as 25% of their body weight on average. Across both trials, about two-thirds of those receiving the active injectable also reported at least a 50% drop in knee OA pain.

Even so, people in the placebo group reported a 38% reduction in OA pain.

Retatrutide is a next-generation triple-hormone receptor agonist and, at this stage, has only been approved by the US Food and Drug Administration for what amounts to compassionate use.

That approval was reportedly granted to only one person in the United States. Still, the findings from these two studies make a strong case for the drug to become the next weight-loss GLP-1 available in the US.

As with earlier obesity treatments, the drug also produced secondary benefits, including lower blood pressure and reduced 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.”

Weight loss on its own can ease knee OA, but unlike single- or dual-receptor drugs such as semaglutide or tirzepatide, retatrutide is injected once a week and activates three natural hormone receptors, which appears to produce greater weight loss.

“Participants had remarkable responses,” Schnitzer says. “Many of the people in this study lost considerable amounts of weight, with a few losing up to a hundred pounds or more.”

The researchers acknowledge that important questions remain, including whether people who are not overweight might also benefit from the pain-relief effects in 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 is also worth noting that some of the study co-authors are scientists who work for Eli Lilly. That is not unusual in an era when companies such as Novo Nordisk are driving much of the progress in metabolic drug development.

The findings from both trials were published in the New England Journal of Medicine.