Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity
Authors' conclusion
In participants with painful knee osteoarthritis and obesity, treatment with retatrutide resulted in significantly greater reductions in both the WOMAC pain score and body weight than placebo. (Funded by Eli Lilly; TRIUMPH-4 and -1 ClinicalTrials.gov numbers, NCT05931367 and NCT05929066.).
Study context
- Population
- Adults without diabetes who had painful knee osteoarthritis and a body-mass index of at least 27participants who underwent randomization, per trial · TRIUMPH-4 445 · TRIUMPH-1-OA 574
- Comparison
- Once-weekly subcutaneous retatrutide vs placebo
- Outcome
- TRIUMPH-4: change in the WOMAC pain score (range, 0 to 10, higher scores indicating worse pain), hybrid-treatment estimand
- Follow-up
- Week 68
Methodological detailsrandomized, placebo-controlled, once-weekly subcutaneous, hybrid-treatment estimand for pain-related end points, treatment-policy strategy for non-pain-related end points, intention-to-treat (ITT) estimand also reported
- Randomized
- Placebo-controlled
- Once-weekly subcutaneous
- Hybrid-treatment estimand for pain-related end points
- Treatment-policy strategy for non-pain-related end points
- Intention-to-treat (ITT) estimand also reported
Main finding
As reported in the abstract
RETATRUTIDE 9 MG
−3.96
mean change
RETATRUTIDE 12 MG
−3.74
mean change
PLACEBO
−2.12
mean change
Estimate (95% CI)P value
RETATRUTIDE 9 MGvs PLACEBOhybrid-treatment estimand
difference vs. placebo −1.83(−2.37 to −1.30)
RETATRUTIDE 12 MGvs PLACEBOhybrid-treatment estimand
difference vs. placebo −1.61(−2.16 to −1.07)
RETATRUTIDE 9 MGvs PLACEBOITT estimand
difference from placebo −1.70(−2.19 to −1.22)
P < 0.001 for all comparisonsRETATRUTIDE 12 MGvs PLACEBOITT estimand
difference from placebo −1.38(−1.91 to −0.85)
P < 0.001 for all comparisonsFurther findings
Mean percent change
| Outcome | RETATRUTIDE 4 MG | RETATRUTIDE 9 MG | RETATRUTIDE 12 MG | PLACEBO | Difference vs. placebo (percentage points) (95% CI) | P value | |
|---|---|---|---|---|---|---|---|
| TRIUMPH-4 (co-primary): percent change in body weight · week 68RETATRUTIDE 9 MGvs PLACEBO | — not stated in the abstract | −20.0% | −23.7% | −4.6% | −15.4 (−18.7 to −12.1) | P < 0.001 for both comparisons | |
| TRIUMPH-4 (co-primary): percent change in body weight · week 68RETATRUTIDE 12 MGvs PLACEBO | −19.2 (−22.4 to −15.9) | P < 0.001 for both comparisons | |||||
| −30−20−10010Difference, percentage points (linear scale) |
— not stated in the abstract
Mean change
| Outcome | RETATRUTIDE 4 MG | RETATRUTIDE 9 MG | RETATRUTIDE 12 MG | PLACEBO | Estimate | P value | |
|---|---|---|---|---|---|---|---|
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 4 MGvs PLACEBOHybrid-treatment estimand | −3.22 | −3.48 | −3.64 | −1.87 | difference vs. placebo −1.35 (95% CI −1.92 to −0.78) | ||
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 9 MGvs PLACEBOHybrid-treatment estimand | difference vs. placebo −1.61 (95% CI −2.20 to −1.02) | ||||||
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 12 MGvs PLACEBOHybrid-treatment estimand | difference vs. placebo −1.77 (95% CI −2.34 to −1.20) | ||||||
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 4 MGvs PLACEBOITT estimand | difference from placebo −0.96 (95% CI −1.61 to −0.30) | P ≤ 0.005 for all comparisons | |||||
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 9 MGvs PLACEBOITT estimand | difference from placebo −1.41 (95% CI −2.07 to −0.75) | P ≤ 0.005 for all comparisons | |||||
| TRIUMPH-1-OA (primary): change in the WOMAC pain score, hybrid-treatment estimand · week 80RETATRUTIDE 12 MGvs PLACEBOITT estimand | difference from placebo −1.64 (95% CI −2.26 to −1.02) | P ≤ 0.005 for all comparisons | |||||
| −3−2−101Difference (linear scale) |
Safety
- In both trials, serious adverse events were more common with retatrutide than with placebo
- The most common adverse events were gastrointestinal
Original publication
Retatrutide Once Weekly in Adults with Knee Osteoarthritis Pain and Obesity. N Engl J Med. Published 8 November 2026. doi:10.
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