TRIUMPH-4: Retatrutide 28.7% Weight Loss in Obesity + Knee OA (December 2025)

Readout date: December 2025 · 68-week Phase 3 trial · 445 participants · Obesity with knee osteoarthritis

TRIUMPH-4 was the first retatrutide Phase 3 trial to report results. Conducted in adults with obesity and knee osteoarthritis, the trial tested 9 mg and 12 mg doses against placebo over 68 weeks. The 12 mg arm produced 28.7% mean body weight loss — the largest mean weight reduction reported in any Phase 3 obesity drug trial at the time of its readout — and significant pain relief.

Headline Results

• Mean weight loss at 12 mg: -28.7% (-32.3 kg / -71.2 lbs) at 68 weeks
• Mean weight loss at 9 mg: -26.4% (-29.1 kg / -64.2 lbs) at 68 weeks
• Placebo: -2.1%
• Systolic blood pressure reduction at 12 mg: -14.0 mmHg
• Knee pain reduction: significant improvement on WOMAC pain subscale
• Discontinuation due to adverse events: 18.2% at 12 mg, 12.2% at 9 mg, 4.0% on placebo

Trial Design

Why TRIUMPH-4 Matters

1. First Phase 3 retatrutide readout. TRIUMPH-4 confirmed that the extraordinary Phase 2 efficacy held at the larger Phase 3 scale. The 28.7% weight loss at 12 mg exceeded the 24.2% seen in the 48-week Phase 2 obesity trial, with the longer duration accounting for additional loss.

2. Two endpoints, two indications. TRIUMPH-4 was designed to support both a weight-management indication and a pain-relief indication for knee osteoarthritis. Both primary endpoints were met — opening a path to two regulatory filings from a single trial.

3. First time the dysesthesia signal emerged. TRIUMPH-4 reported a dose-dependent dysesthesia signal — 20.9% at 12 mg, 8.8% at 9 mg, 0.7% on placebo — that had not been observed in Phase 2 retatrutide trials. This is now the most-watched safety signal across the program. See our side effects page for details.

4. Cardiometabolic effects in line with the class. The 14.0 mmHg reduction in systolic blood pressure at 12 mg, along with improvements in lipids and inflammatory markers (hsCRP), reinforces that retatrutide's cardiometabolic profile matches or exceeds tirzepatide and semaglutide.

Weight Loss by Dose

Safety: TRIUMPH-4 Adverse Event Rates

GI symptoms dominated the safety profile, consistent with the GLP-1 class. The dysesthesia signal — an abnormal skin-prickling/tingling sensation — was the most distinctive finding and was dose-dependent.

For a full safety analysis, see our side effects page.

What Comes Next

• Full peer-reviewed publication of TRIUMPH-4 is expected with additional secondary endpoints and body composition data.
• Combined with TRIUMPH-3 (Mar 2026) and TRANSCEND-T2D-1 (Mar 2026), three of the major retatrutide Phase 3 trials have now reported.
• TRIUMPH-1 and TRIUMPH-2 — the larger obesity-population trials — are still expected to read out in 2026.
• FDA filing is expected in 2026 per Lilly guidance, supporting obesity, knee OA, OSA, and potentially type 2 diabetes indications. See our FDA approval timeline.

Frequently Asked Questions

Sources

• Eli Lilly and Company. (December 2025). Lilly's retatrutide achieved significant weight loss and pain relief in adults with obesity and knee osteoarthritis. Press release

Medical disclaimer: Retatrutide is not FDA approved and is not available outside of clinical trials. This page is informational only, not medical advice. Always consult a qualified healthcare provider before making decisions about medications. glp3.wiki is not affiliated with Eli Lilly or any pharmaceutical company.