Two Phase 3 clinical trials involving more than 1,000 adults found that people prescribed high doses of Eli Lilly's experimental GLP-1-based drug retatrutide lost, on average, up to 25% of their body weight, while around two-thirds receiving the active injectable reported at least a 50% reduction in knee osteoarthritis pain, strengthening the case for the drug to gain FDA approval for weight loss and knee osteoarthritis relief.
The studies, led by Northwestern University and published in the New England Journal of Medicine, tested a once-weekly injection of retatrutide, a next-generation triple-hormone receptor agonist. Those receiving a placebo self-reported a 38% reduction in knee osteoarthritis pain.
Retatrutide is so far only approved by the US Food and Drug Administration for what equates to compassionate use, which was reportedly granted to one American. The results form a good case for the drug to become the next weight-loss GLP-1 on the US market. Like other obesity medications, it also showed secondary benefits including 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,” said 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.”
Unlike single- or dual-receptor drugs such as semaglutide or tirzepatide, retatrutide activates three natural hormone receptors, resulting in a higher percentage of weight loss. “Participants had remarkable responses,” he said. “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 acknowledged that questions remain, including whether people who are not overweight can benefit from the pain-relief aspect. “These drugs are believed to have significant anti-inflammatory activity, but the mechanism is not entirely known,” Schnitzer added. “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 was noted that study co-authors include scientists who also work for Eli Lilly, which is not unusual in the field of metabolic drug development.
Analysis
Why This Matters
- The results offer a potential new treatment option for the millions of people with knee osteoarthritis who are also overweight, addressing both weight and pain in one drug.
- Retatrutide's higher weight-loss effect compared to existing GLP-1 drugs could make it a leading candidate for obesity treatment if approved.
- The findings may open new avenues for research into the anti-inflammatory properties of this class of drugs and their role in joint health.
Background
Knee osteoarthritis is a common condition causing pain and stiffness, often linked to excess body weight. GLP-1 receptor agonists are a class of drugs originally developed for type 2 diabetes that have been shown to produce significant weight loss. Retatrutide is a newer, triple-agonist version that targets three natural hormone receptors, potentially offering greater weight-loss effects than earlier drugs.
Key Perspectives
Dr. Thomas Schnitzer, Northwestern University: said the findings show that for overweight people with OA, significant weight loss from the treatment can lead to meaningful pain reduction, but added that more research is needed on whether the drug's anti-inflammatory effects also play a role.
Study co-authors from Eli Lilly: contributed to the research, which is typical for industry-led drug development.
What to Watch
- The FDA's decision on whether to approve retatrutide for weight loss and osteoarthritis.
- Further studies exploring the drug's anti-inflammatory effects and its benefit for people without excess weight.
- Ongoing monitoring of long-term efficacy and safety as the drug moves toward broader use.
Checked
12 claims in this story checked against 1 source: 12 supported.
Show each claim
- SupportedThe headline says trials show retatrutide could relieve knee osteoarthritis pain.New Atlas: Technology-Innovation-Outdoor News: “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).”
- SupportedThe summary says high-dose retatrutide recipients lost, on average, up to 25% of their body weight.New Atlas: Technology-Innovation-Outdoor News: “people prescribed high doses of retatrutide lost, on average, up to 25% of their body weight”
- SupportedThe summary says around two-thirds of active-injection recipients reported at least a 50% reduction in knee pain.New Atlas: Technology-Innovation-Outdoor News: “across both studies, around two-thirds receiving the active injectable also reported at least a 50% reduction in knee OA pain”
- SupportedThomas Schnitzer said, “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.”New Atlas: Technology-Innovation-Outdoor News: ““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”
- SupportedSchnitzer said, “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.”New Atlas: Technology-Innovation-Outdoor News: ““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.””
- SupportedThe story says Schnitzer described participants as having “remarkable responses.”New Atlas: Technology-Innovation-Outdoor News: ““Participants had remarkable responses,” notes Schnitzer.”
- SupportedSchnitzer said some participants lost “up to a hundred pounds or more.”New Atlas: Technology-Innovation-Outdoor News: ““Many of the people in this study lost considerable amounts of weight, with a few losing up to a hundred pounds or more.””
- SupportedSchnitzer said, “These drugs are believed to have significant anti-inflammatory activity, but the mechanism is not entirely known.”New Atlas: Technology-Innovation-Outdoor News: ““These drugs are believed to have significant anti-inflammatory activity, but the mechanism is not entirely known,” Schnitzer adds.”
- SupportedSchnitzer said more research is needed on whether reducing joint inflammation matters in addition to reducing load.New Atlas: Technology-Innovation-Outdoor News: ““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.””
- SupportedThe story says two Phase 3 trials involved more than 1,000 adults.New Atlas: Technology-Innovation-Outdoor News: “Two Phase 3 clinical trials that involved more than 1,000 adults”
- SupportedThe story says the studies strengthened the case for retatrutide to gain FDA approval for weight loss and knee osteoarthritis relief.New Atlas: Technology-Innovation-Outdoor News: “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).”
- SupportedThe story says placebo recipients self-reported a 38% reduction in knee osteoarthritis pain.New Atlas: Technology-Innovation-Outdoor News: “those receiving the placebo self-reported a 38% reduction in OA pain.”
