A powerful experimental weight-loss drug significantly reduced knee pain in people with obesity and moderate osteoarthritis, according to results from two large Phase 3 clinical trials published this week. Participants who injected retatrutide for 68 to 80 weeks lost as much as 24% of their body weight while reporting substantially less knee pain and better physical function.
The findings, first reported by the NZ Herald, come from a Northwestern University-led study pooling data from two trials that together recruited hundreds of men and women with obesity and moderate knee arthritis, none of whom had diabetes. Eli Lilly, the drug's manufacturer, is expected to apply for United States FDA approval early next year, and for the first time in the GLP-1 drug class that application would include knee osteoarthritis as a treatment indication.
What the retatrutide trials found
Retatrutide is what scientists call a triple-hormone-receptor-agonist. In plain terms, it mimics three hormones involved in weight regulation, including GLP-1, or glucagon-like peptide 1. It remains investigational, meaning it has not yet been approved by the US Food and Drug Administration, but it has produced some of the largest weight declines of any GLP-1-related drug tested to date.
Researchers randomly assigned participants to a placebo or to one of several doses of retatrutide, then tracked body weight, knee pain, physical function such as rising from the floor or using stairs, and metabolic health over 68 or 80 weeks.
The drug was very effective on both fronts, said Thomas Schnitzer, a rheumatologist at Northwestern University's Feinberg School of Medicine who led the study. Almost everyone on the drug moved and functioned better by the end, and markers of metabolic health, including blood pressure and inflammatory proteins, improved as well.
According to U.S. News, between 64% and 65% of retatrutide patients achieved at least a 50% improvement in knee function, compared with 33% of those on a placebo. Northwestern Now reported that participants lost up to 25% of their body weight, and about two-thirds saw their knee pain fall by at least half.
Why the pain relief puzzles scientists
The most intriguing result is also the hardest to explain. People on the highest doses lost the most weight, but knee pain improved by roughly the same amount regardless of dose. Many participants also reported that knee benefits plateaued about halfway through the study, even as they continued shedding weight for months afterwards.
The mismatch between pain and weight is intriguing, said Jay Karri, an assistant professor of neurology and orthopaedics at the University of Maryland School of Medicine, who has studied GLP-1 drugs and arthritis but was not involved in the new experiments.
These trials confirm that powerful weight-loss drugs such as the GLP-1s can give people with knee osteoarthritis and obesity pain relief at least as good as our best current medicines.
Karri noted that most participants started with only moderate arthritic pain, which may have capped how much improvement was possible to measure. Alternatively, the drug's effects on joints may simply run on a different timetable than its effects on body weight.
Could GLP-1 drugs treat arthritis directly?
The central unanswered question is whether the knee benefits came from carrying less weight, or whether retatrutide acted directly inside the joints, perhaps by lowering inflammation or protecting cartilage.
The idea is biologically plausible, said Kristen Mathias, a rheumatologist at Johns Hopkins University School of Medicine who was not involved in the research. Knees contain receptors that respond to GLP-1, and in mouse studies GLP-1-agonist drugs improved cartilage and other joint tissues even when the animals lost no weight.
The FDA has also fast-tracked a study injecting a GLP-1 drug, not retatrutide, directly into the knees of people with severe arthritis pain. That trial should clarify whether the benefits can be localized, but even with expedited review it is likely to take years.
Schnitzer acknowledged the new study was not designed to answer how the drug eased knee pain, though it is certainly possible it worked both by lowering weight and by changing the environment inside the knee. The trials did not include scans of joint structure, and further studies are needed.
A widening picture of GLP-1 benefits
The retatrutide results build on a growing body of evidence that GLP-1 drugs deliver health benefits well beyond weight loss, including reduced risks of heart disease, sleep apnoea and some cancers. Earlier GLP-1s have been linked to fewer total knee replacements among people with obesity and arthritis.
If retatrutide proves to act directly on joints, it could eventually become a treatment option for people with arthritis regardless of whether they want or need to lose weight, a shift that would change how rheumatologists approach a condition affecting hundreds of thousands of New Zealanders.
Frequently asked questions
What is retatrutide?
Retatrutide is an experimental injectable drug that mimics three weight-related hormones, including GLP-1. It is not yet approved by the FDA, and Eli Lilly is expected to seek approval for obesity, Type 2 diabetes and knee osteoarthritis early next year.
How much knee pain relief did participants report?
About two-thirds of those taking retatrutide experienced at least a 50% reduction in knee pain, compared with roughly one-third of placebo patients, according to the pooled trial results.
Is retatrutide available in New Zealand?
No. The drug is still investigational and has not been approved by the FDA or by New Zealand's medicines regulator. Approval applications are expected in early 2027.