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

Property	Value
Trial Name	TRIUMPH-1
Phase	3
Status	results-published
Enrollment	2,339 participants
Start Date	October 1, 2023
Completion	April 1, 2026
Conditions	obesity, overweight
Primary Endpoints	Percent change in body weight from baseline at 80 weeks; Proportion of participants achieving ≥5% weight loss at 80 weeks

Study Overview

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

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. This makes TRIUMPH-1 the most directly comparable retatrutide trial to SURMOUNT-1 (tirzepatide) and STEP-1 (semaglutide 2.4 mg).

Trial Design

Element	Detail
Design	Randomized, double-blind, placebo-controlled, multicenter
Randomization	1:1:1:1 (4 mg / 9 mg / 12 mg / placebo)
Enrollment	2,339 adults
Mean baseline BMI	40.0 kg/m²
Mean baseline weight	112.7 kg (248.5 lbs)
Treatment duration	80 weeks (primary) + 24-week extension to 104 weeks
Dose escalation	Stepwise every 4 weeks (2 mg → 4 mg → 6 mg → 9 mg → 12 mg)
Permanent dose reduction	Permitted for GI adverse-event management

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

Primary Endpoint: Weight Loss at 80 Weeks

Dose	Efficacy estimand	Treatment-regimen estimand
Placebo	-2.2% (-5.5 lbs)	-3.9% (-9.7 lbs)
4 mg	-19.0% (-47.2 lbs)	-17.6% (-43.7 lbs)
9 mg	-25.9% (-64.4 lbs)	-23.7% (-58.9 lbs)
12 mg	-28.3% (-70.3 lbs)	-25.0% (-62.1 lbs)

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

Responder analysis (12 mg arm, 80 weeks)

Threshold	12 mg	9 mg	4 mg	Placebo
≥25% weight loss	62.5%	52.9%	27.8%	2.2%
≥30% weight loss	45.3%	37.9%	15.3%	0.5%
≥35% weight loss	27.2%	20.8%	5.9%	0.3%
BMI <30 (no longer obese)	65.3%	—	—	—

Among the 12 mg arm specifically, 65.3% ended the trial with a BMI below 30 — moving from obesity to 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).

Dose	Reduction at 80 weeks
Placebo	-3.6 cm (-1.4 in)
4 mg	-16.3 cm (-6.4 in)
9 mg	-21.8 cm (-8.6 in)
12 mg	-24.1 cm (-9.5 in)

Extension Phase (Through 104 Weeks)

A 532-participant extension among those with baseline BMI ≥35 evaluated whether weight loss continued, plateaued, or regressed past the 80-week primary endpoint. Placebo and lower-dose participants were transitioned to maximum tolerated dose (MTD) at week 80.

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

Arm	Mean weight loss at 104 wk
4 mg → MTD	-27.9% (-73.3 lbs)
9 mg → MTD	-29.5% (-80.7 lbs)
12 mg	-30.3% (-85.0 lbs)
Placebo → MTD	-19.2% (-49.9 lbs)

The 12 mg arm crossed 30% mean weight loss at 104 weeks in this higher-BMI subgroup — bariatric-surgery territory. Notably, participants switched from placebo to retatrutide MTD lost 19.2% in the 24-week extension, demonstrating that retatrutide produces rapid weight loss even after a long placebo run-in.

Safety Profile

Dysesthesia (the headline neurological signal)

Dose	Dysesthesia incidence
Placebo	0.9%
4 mg	5.1%
9 mg	12.3%
12 mg	12.5%

A critical comparison: TRIUMPH-1 dysesthesia at 12 mg was 12.5%, versus 20.9% in TRIUMPH-4 at the same dose. The difference may reflect the older, higher-comorbidity, knee-OA-specific TRIUMPH-4 population, or population-level differences in nerve sensitivity to glucagon-receptor-mediated metabolic shifts. Most cases were mild-to-moderate, primarily occurred during dose escalation, and the majority of affected participants continued treatment.

Gastrointestinal adverse events

Consistent with the incretin class, broadly comparable to TRIUMPH-4:

Event	4 mg	9 mg	12 mg	Placebo
Nausea	28.6%	38.4%	42.4%	14.8%
Diarrhea	25.2%	34.1%	32.0%	13.5%
Vomiting	10.6%	22.8%	25.3%	4.8%
Constipation	23.8%	25.9%	26.1%	10.9%

Other adverse events of interest

Event	4 mg	9 mg	12 mg	Placebo
Urinary tract infection	7.5%	8.8%	8.4%	5.3%
Upper respiratory tract infection	14.2%	12.2%	13.1%	11.6%

Treatment discontinuation due to adverse events

Dose	Discontinuation rate
4 mg	4.1%
9 mg	6.9%
12 mg	11.3%
Placebo	4.9%

The 12 mg discontinuation rate of 11.3% is meaningfully higher than placebo, but lower than the 18.2% reported in TRIUMPH-4 at the same dose — again consistent with the lower-comorbidity, broader-obesity TRIUMPH-1 population tolerating the drug better.

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 mean weight loss reported in a Phase 3 trial in adults with obesity but without type 2 diabetes or osteoarthritis comorbidity. It substantially exceeds tirzepatide’s -22.5% in SURMOUNT-1 (15 mg, 72 weeks) and semaglutide 2.4 mg’s -14.9% in STEP-1 (68 weeks), positioning retatrutide as the most efficacious chronic-weight-management agent in pivotal Phase 3 testing.

Bariatric-surgery-range outcomes in a meaningful minority

The 45.3% of 12 mg participants achieving ≥30% weight loss approaches outcomes historically associated only with sleeve gastrectomy or Roux-en-Y gastric bypass. This is the first chronic-weight-management drug to demonstrate this magnitude of effect in a pivotal trial.

Implications for the safety label

The lower dysesthesia rate versus TRIUMPH-4 will be reassuring to regulators, though dysesthesia remains a class-distinguishing finding (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 obesity-indication anchor trial. With this readout in hand, Eli Lilly retains its previously communicated guidance for an NDA filing in late 2026 to Q1 2027, with potential approval in late 2027 or early 2028. Read in combination with the Foundayo (orforglipron) FDA approval in April 2026 and Mounjaro/Zepbound’s ongoing growth, Lilly’s anti-obesity franchise spans oral, weekly-injectable, and now the triple-agonist next generation.

Publication Status

Topline results announced via Eli Lilly press release on May 21, 2026. Full data are expected to be presented at a major medical meeting later in 2026 (likely ADA 2026 in June or ObesityWeek 2026) and submitted for peer-reviewed publication. The TRIUMPH-2 (obesity + type 2 diabetes) readout is expected in Q2-Q3 2026, and TRIUMPH-3 (obesity + established cardiovascular disease) in Q3-Q4 2026.