Redefining Knee Osteoarthritis Management: The Role of Retatrutide

In the TRIUMPH-4 trial, retatrutide produced mean weight loss up to 28.7% at 68 weeks and an average 75.8% reduction in WOMAC pain versus placebo — effect sizes that, if confirmed, could reshape care for obesity-related knee osteoarthritis.

Prior weight-loss approaches typically yielded single-digit or low double-digit mean weight changes and showed inconsistent effects on osteoarthritis pain and function. By contrast, TRIUMPH-4 reports much larger, sustained weight reductions occurring alongside large symptomatic gains, signaling a potential shift in expectations for symptom modification in this population. Adults with obesity and symptomatic knee osteoarthritis are therefore the primary group likely to be affected.

TRIUMPH-4 was a randomized, phase 3, 68-week study; retatrutide was evaluated against placebo with co-primary endpoints of percent weight change and WOMAC pain at week 68. The study reports mean weight reductions up to 28.7% at 68 weeks versus minimal change on placebo.

The co-primary pain endpoint used the WOMAC pain subscale and showed an average reduction of 75.8%, described as clinically and statistically meaningful versus placebo. Physical function measures improved substantially alongside pain scores, reflecting gains in mobility and daily activities for many participants. The magnitude of pain relief plausibly reflects biomechanical unloading from weight loss together with symptomatic effects of the therapy.

Safety findings align with incretin-class tolerability profiles: higher rates of gastrointestinal events (nausea, diarrhea, constipation, vomiting) and more frequent reports of dysesthesia were observed in active arms than placebo, and adverse-event–related discontinuations were dose-related.