An experimental Eli Lilly drug, retatrutide, reduced knee osteoarthritis pain and body weight in two phase 3 clinical trials, researchers said on Sunday.
Retatrutide Reduces Knee Osteoarthritis Pain and Improves Function
Researchers presented the findings at the American College of Rheumatology annual meeting. The studies were titled “Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity.”, according to Yahoo Finance
“We saw very exciting amounts of pain reduction and function improvement over time. I think this is a big advance… Osteoarthritis has lacked effective therapies for so long,” study investigator Philip Conaghan, MBBS, PhD, director of the NIHR Biomedical Research Centre in Leeds and professor of musculoskeletal medicine at the University of Leeds, United Kingdom, told Medscape Medical News.
More than 1,000 participants took part in two trials, TRIUMPH-4 and TRIUMPH-1-OA. In TRIUMPH-4, 445 people were assigned to 9-mg or 12-mg doses or placebo for 68 weeks.
$LLY – Eli Lilly: Retatrutide Cuts Knee Pain by Up to 76% in Phase 3 Trials, Taltz-Zepbound Combination Shows Strong Results ⠀ • TRIUMPH-4: Retatrutide reduced knee osteoarthritis pain by up to 75.8% over 68 weeks, with more than 1 in 8 patients reporting no knee pain. •…
In TRIUMPH-1-OA, 574 people were assigned to 4-mg, 9-mg, or 12-mg doses or placebo. Data pooled from the trials showed that about two-thirds of patients taking retatrutide achieved at least a 50 percent reduction in knee pain by week 68. This compared with 38 percent of those in the placebo group.
Physical function also improved by at least half in roughly 64 percent of the treatment group. Only 33 percent of the placebo group saw this improvement. Participants on the highest doses lost up to 25 percent of their body weight on average.
The research team assessed pain using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) Pain Index. This measures pain on a scale of 0 to 10. Participants also logged daily pain ratings with an app.
Weight Loss Eases Knee Pain
“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,” Thomas Schnitzer said.
Some participants lost 100 pounds or more. Schnitzer said many participants had remarkable responses.
🚨 BREAKING: Lilly's retatrutide helped people lose about 25% of their body weight in a big phase 3 trial, and it eased knee pain too!
The reduction in weight likely lowers the mechanical load on the knee joint. “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,” Schnitzer said.
Participants also experienced improvements in blood pressure, lipid levels, and systemic inflammation. Experts say it is unclear how much pain relief comes from mechanical unloading versus the drug’s potential anti-inflammatory effects within the joint.
Gastrointestinal Side Effects Occur During Dose Escalation
Researchers observed gastrointestinal side effects, particularly during the dose-escalation phase. Serious adverse events occurred in 9.5 percent, 10.8 percent, and 2.0 percent of participants in the 9-mg, 12-mg, and placebo groups, respectively.
Adverse events leading to study discontinuation occurred in 12.9 percent, 18.2 percent, and 4.0 percent of those groups, respectively. The U.S. Food and Drug Administration has not approved retatrutide for the treatment of osteoarthritis.
The drug is a triple agonist targeting GLP-1, GIP, and glucagon receptors. This distinguishes it from medications that target one or two receptors.
Millions live with painful arthritic knees. A new shot just erased that pain in two large clinical trials. Two phase 3 trials, together involving more than 1,000 adults with knee osteoarthritis and overweight or obesity, tested the once-weekly injection against a placebo. And… pic.twitter.com/H1dCmCrFgq
Timothy Gibson is the medical director of the MemorialCare Joint Replacement Center at Orange Coast Medical Center. He said the results were notable because “retatrutide appears capable of producing the degree of weight reduction that may translate into less knee pain and improved mobility.”
Questions About Long-Term Health
Questions remain about how the drug impacts joint health over the long term. The trials excluded people already requiring joint replacement.
It is not yet confirmed if the medication can slow the progression of osteoarthritis or prevent the need for surgery. People should consult with healthcare professionals regarding chronic joint pain and weight management. Diet, exercise, and lifestyle modifications are the foundational care for people with knee osteoarthritis.
