TRIUMPH-1: Phase 3 Pivotal Obesity Trial of Retatrutide (Results-Published)

Study Overview

TRIUMPH-1 is the pivotal Phase 3 obesity trial of retatrutide in adults without type 2 diabetes. Eli Lilly announced topline results on May 21, 2026, the second positive Phase 3 readout in the TRIUMPH program after TRIUMPH-4 (knee osteoarthritis subpopulation). With 2,339 participants across all four arms, TRIUMPH-1 is retatrutide’s largest pivotal weight-loss readout and will anchor Eli Lilly’s regulatory filings for chronic weight management.

The trial enrolled adults with obesity or overweight plus at least one weight-related comorbidity (hypertension, dyslipidemia, sleep apnea or knee osteoarthritis) but without diabetes. That makes TRIUMPH-1 the retatrutide trial most directly comparable to SURMOUNT-1 (tirzepatide) and STEP-1 (semaglutide 2.4 mg).

Trial Design

The 80-week primary timepoint is longer than the 68 weeks used in TRIUMPH-4 and in the SURMOUNT and STEP pivotal trials, so more of the weight-loss curve has time to play out.

Primary Endpoint: Weight Loss at 80 Weeks

All three doses met the primary endpoint with statistical significance versus placebo.

Responder analysis (12 mg arm, 80 weeks)

In the 12 mg arm, 65.3% ended the trial with a BMI below 30, moving from obesity into the overweight or normal-weight range. Among those with a baseline BMI ≥40 (severe obesity), 37.5% reached BMI <30.

Secondary Endpoint: Waist Circumference

Baseline mean waist circumference was 118.3 cm (46.6 inches).

Extension Phase (Through 104 Weeks)

A 532-participant extension in people with baseline BMI ≥35 tested whether weight loss continued, leveled off or reversed after the 80-week primary endpoint. Placebo and lower-dose participants moved to the maximum tolerated dose (MTD) at week 80.

Efficacy estimand at 104 weeks (BMI ≥35 subgroup):

The 12 mg arm passed 30% mean weight loss at 104 weeks in this higher-BMI subgroup, a level usually associated with bariatric surgery. Participants switched from placebo to retatrutide MTD lost 19.2% in the 24-week extension, showing that retatrutide produces rapid weight loss even after a long time on placebo.

Safety Profile

Dysesthesia (the headline neurological signal)

The key comparison: TRIUMPH-1 dysesthesia at 12 mg was 12.5%, versus 20.9% in TRIUMPH-4 at the same dose. The gap may reflect TRIUMPH-4’s older, higher-comorbidity, knee-OA-specific population, or population differences in how sensitive nerves are to glucagon-receptor-driven metabolic shifts. Most cases were mild to moderate and occurred mainly during dose escalation, and most affected participants continued treatment.

Gastrointestinal adverse events

As expected for the incretin class, and broadly similar to TRIUMPH-4:

Other adverse events of interest

Treatment discontinuation due to adverse events

The 12 mg discontinuation rate of 11.3% is clearly higher than placebo but lower than the 18.2% reported in TRIUMPH-4 at the same dose. This again fits the idea that TRIUMPH-1’s broader obesity population, with fewer comorbidities, tolerated the drug better.

Nested Comorbidity Baskets (ADA 2026)

When the full TRIUMPH-1 data were presented at the ADA 2026 Scientific Sessions on June 6, 2026, the nested comorbidity sub-studies showed benefits beyond weight. Because TRIUMPH-1 enrolled people with weight-related comorbidities, it included basket analyses for two of the most burdensome conditions:

Lilly’s June 2026 release reported the sleep apnea reduction of up to 60.6% without naming a dose. The NEJM paper (October 20, 2026) shows the largest AHI reduction at 9 mg (-34.3 events per hour, against -31.7 at 12 mg); see retatrutide and sleep apnea.

These results across several conditions matter for the regulatory strategy. The knee osteoarthritis benefit echoes the dedicated TRIUMPH-4 trial (WOMAC pain -75.8% at 9 mg), and the 60.6% drop in apnea-hypopnea index puts retatrutide head to head with tirzepatide’s OSA indication (SURMOUNT-OSA). Eli Lilly has signaled it plans to seek labeling for obesity, obstructive sleep apnea and knee osteoarthritis, and the TRIUMPH-1 baskets supply supporting evidence for all three in one trial.

Clinical Significance

Largest weight-loss readout to date in the obesity-only population

The 28.3% mean weight loss at 12 mg in TRIUMPH-1 is the highest reported in a Phase 3 trial in adults with obesity but without type 2 diabetes or osteoarthritis comorbidity. It is well above tirzepatide’s -22.5% in SURMOUNT-1 (15 mg, 72 weeks) and semaglutide 2.4 mg’s -14.9% in STEP-1 (68 weeks), making retatrutide the most effective chronic weight management drug tested in pivotal Phase 3 trials.

Bariatric-surgery-range outcomes in a meaningful minority

The 45.3% of 12 mg participants who lost ≥30% of their weight approach results historically seen only with sleeve gastrectomy or Roux-en-Y gastric bypass. No chronic weight management drug had shown an effect this large in a pivotal trial before.

Implications for the safety label

The lower dysesthesia rate compared with TRIUMPH-4 will reassure regulators, though dysesthesia still sets retatrutide apart from its class (semaglutide and tirzepatide do not report this signal). The labeled discontinuation rate is likely to be ~10-12% at the highest dose.

Regulatory and competitive significance

TRIUMPH-1 is the anchor trial for the obesity indication. With TRIUMPH-2 and TRIUMPH-3 reported on July 23, 2026, the obesity package is complete, and Eli Lilly says it plans to file for approval no later than Q1 2027; on our estimate, a decision could come in late 2027 with priority review or around Q1 2028 with standard review. The FDA ruled on October 2, 2026 that retatrutide is a drug, so the application must be a New Drug Application (NDA); Lilly disputes that in court and has not said which pathway it will use (the FDA ruling). Within the wider program, TRIUMPH-1 contributes the largest weight-loss result and the largest population without diabetes.

Publication Status

Topline results were announced in an Eli Lilly press release on May 21, 2026, and the full data were presented at the ADA 2026 Scientific Sessions on June 6, 2026 in New Orleans, as part of the symposium “Unlocking the Next Frontier in Treatment of Obesity and Type 2 Diabetes with Retatrutide.” The peer-reviewed paper was published in the New England Journal of Medicine on September 29, 2026 (Jastreboff et al., doi 10.1056/NEJMoa2604169), and the sleep apnea basket results followed in a separate NEJM paper on October 20, 2026 (Grunstein et al.). The companion TRANSCEND-T2D-1 diabetes trial was published in The Lancet at the same time as the ADA presentation. The remaining core obesity readouts, TRIUMPH-2 (obesity + type 2 diabetes) and TRIUMPH-3 (obesity + established cardiovascular disease), reported topline results on July 23, 2026. No application has been filed yet; Lilly says it plans to file no later than the first quarter of 2027.