Does Retatrutide Help Knee Osteoarthritis? The Short Answer

In its trials, retatrutide reduced knee pain in people with obesity and knee osteoarthritis much more than placebo. In TRIUMPH-4, the first Phase 3 retatrutide trial to report results, knee pain fell by up to 75.8% over 68 weeks if taken as intended, compared with 40.3% on placebo, alongside weight loss of up to 28.7%. Counting everyone randomized, pain fell by up to 67.2%, and 14.1% of people on 9 mg were completely free of knee pain at the end, compared with 4.2% on placebo. A group of 574 people with knee osteoarthritis inside the larger TRIUMPH-1 trial showed the same direction of effect.

Retatrutide is an investigational weight-loss medicine, not a treatment for arthritis, and it is not approved for any use. The trials tested whether it reduces knee pain in people with obesity; they did not test whether it changes the joint itself.

How TRIUMPH-4 Was Designed

TRIUMPH-4 enrolled 445 adults with a BMI of 27 or more and knee osteoarthritis: knee pain for more than 12 weeks and Kellgren-Lawrence grade 2 or 3 changes on X-ray. People with type 1 or type 2 diabetes were excluded. Participants were randomly assigned in equal numbers to once-weekly retatrutide 9 mg or 12 mg, or placebo, for 68 weeks.

On average they weighed 112.7 kg (248.5 lb) with a BMI of 40.4, and 84% had a BMI of 35 or more. Their average knee pain score at the start was 6.0 on the WOMAC pain scale. The trial had two co-primary end points: percent change in body weight and change in WOMAC pain at week 68.

The developer announced the topline results on December 11, 2025. As of October 2026, we found no peer-reviewed publication of the full results; the figures below come from the company's announcement and its medical information summary.

Knee Pain and Physical Function

The WOMAC index is a standard questionnaire for knee and hip osteoarthritis. The company reported results in two ways: counting everyone randomized (the treatment-regimen estimand) and as if everyone had stayed on treatment (the efficacy estimand). The headline 75.8% is the efficacy figure for 9 mg. The pre-specified end point was the change in points; the company says the percentage changes were estimated in a post hoc analysis.

Pain fell numerically slightly more on 9 mg than on 12 mg, although the 12 mg group lost more weight. In a post hoc analysis, 14.1% of people on 9 mg and 12.0% on 12 mg were completely free of knee pain at 68 weeks, compared with 4.2% on placebo. Physical function on the WOMAC scale improved by 4.1 points (71.8%) on 9 mg and 4.2 points (73.7%) on 12 mg, compared with 2.1 points (35.6%) on placebo (efficacy estimand).

Weight Loss in TRIUMPH-4

Among people on 12 mg, 58.6% lost at least 25% of their body weight, 39.4% at least 30% and 23.7% at least 35% (efficacy estimand), compared with 1.3%, 0.8% and 0% on placebo. The company also reported reductions in non-HDL cholesterol, triglycerides and hsCRP, and a 14.0 mmHg fall in systolic blood pressure on the highest dose (efficacy estimand). These results and the weight-loss thresholds above were not controlled for multiple testing.

Side Effects in TRIUMPH-4

Dysesthesia, an abnormal skin sensation, was reported by 20.9% of people on 12 mg, higher than with 12 mg in TRIUMPH-1 (12.5%) and in the two diabetes trials (4.4% and 7.3%); the company described it as generally mild and said it rarely led to stopping treatment.

The company said discontinuations were highly correlated with baseline BMI and included people who stopped because they felt they had lost too much weight. Among the 84% of participants with a BMI of 35 or more, 8.8% on 9 mg and 12.1% on 12 mg stopped because of side effects, compared with 4.8% on placebo.

Knee Results From TRIUMPH-1

TRIUMPH-1, the larger Phase 3 obesity trial published in the New England Journal of Medicine in September 2026, included 574 participants with moderate or severe knee osteoarthritis. After 80 weeks, WOMAC pain fell by 3.5 points on 9 mg and 3.6 points on 12 mg, compared with 1.9 points on placebo, according to the published paper. The company's June 2026 announcement, using the efficacy estimand, gave a reduction of up to 73.1%.

Does Retatrutide Treat the Arthritis Itself?

The trials do not show that. They measured pain and physical function, which improved, but neither the TRIUMPH-4 announcement nor the TRIUMPH-1 paper reports changes in the joint structure, such as cartilage, on imaging. Weight loss reduces the load on the knee, and the trials do not separate how much of the pain relief came from weight loss and how much from anything else. TRIUMPH-4 compared retatrutide only with placebo, not with other osteoarthritis treatments.

What Is Still Unknown

• The full peer-reviewed results of TRIUMPH-4.
• Whether pain relief lasts after stopping retatrutide (see weight regain after stopping retatrutide).
• Whether retatrutide affects the joint itself or only the symptoms.
• How it compares with other osteoarthritis treatments or other weight-loss medicines.

Lilly plans to submit retatrutide to the US Food and Drug Administration in the first quarter of 2027. Which uses that application will cover has not been announced.

Sources

• Eli Lilly. Lilly's triple agonist, retatrutide, delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful Phase 3 trial. December 11, 2025. (TRIUMPH-4)
• Lilly Medical. TRIUMPH-4 trial summary (retatrutide in obesity and knee osteoarthritis).
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1, knee substudy)
• Eli Lilly. Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications. June 6, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.

Medical Disclaimer: This article summarizes clinical trial results for general information only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. Nothing here is a recommendation to use, seek out or avoid any medication or treatment.