TRIUMPH-1 Results at a Glance
TRIUMPH-1 is the main Phase 3 obesity trial of retatrutide, an investigational weekly injection that acts on GIP, GLP-1 and glucagon receptors. Its developer announced the topline results on May 21, 2026, and the full results were published in the New England Journal of Medicine on September 29, 2026 (Jastreboff, Kaplan, Davies et al.).
- At 80 weeks, people on the highest dose, 12 mg, lost 25.0% of their body weight on average, counting everyone randomized, compared with 3.9% on placebo.
- Among people who stayed on treatment as intended, the 12 mg average was 28.3%, compared with 2.2% on placebo.
- Counting everyone randomized, 36.9% of the 12 mg group lost at least 30% of their weight, compared with 0.6% on placebo.
- All primary and key secondary end points were met.
- Side effects were mostly gastrointestinal. Adverse events led 11.2% of the 12 mg group to stop treatment, compared with 4.6% on placebo.
How the TRIUMPH-1 Trial Was Designed
The trial enrolled 2,339 adults at 131 sites in 11 countries. Participants had obesity (a BMI of 30 or more, or 27 to under 30 with at least one weight-related condition) and did not have diabetes. On average they weighed about 112 to 113 kg (roughly 248 lb), had a BMI of about 40, and about 65% were women.
Participants were randomly assigned in equal numbers to once-weekly retatrutide 4 mg, 9 mg or 12 mg, or placebo, for 80 weeks, followed by 4 weeks of follow-up. Doses were increased step by step until each person reached the assigned dose. The primary end point was the percent change in body weight at week 80 with 9 mg and 12 mg compared with placebo.
The trial also included two groups of participants studied for specific conditions: 574 people with moderate or severe knee osteoarthritis and 243 with obstructive sleep apnea.
Two Ways of Counting the Results
The paper reports results in two ways, and the difference matters whenever TRIUMPH-1 numbers are quoted. The treatment-regimen estimand counts everyone who was randomized, including people who stopped the drug. The efficacy estimand estimates what would have happened if everyone had stayed on treatment as intended. The second always gives larger numbers. The company's announcement led with the 28.3% efficacy figure; this article gives both, and labels which is which.
Weight Loss by Dose
Weight loss rose with dose. The difference between 9 mg and 12 mg was smaller than the difference between 4 mg and 9 mg. How the loss built up over the 80 weeks is covered in the retatrutide weight loss timeline.
How Many People Reached Each Weight-Loss Threshold
Averages hide how much results varied between people. The paper reports the share of each group that reached each threshold, counting everyone randomized.
The May announcement gave higher figures for the 12 mg group (62.5% reaching at least 25%, 45.3% at least 30% and 27.2% at least 35%). Those use the efficacy estimand, so they are not directly comparable with the table above.
The paper also reports that, counting everyone randomized, 40.1% to 57.1% of people across the three retatrutide groups reached a BMI below 30, compared with 9.2% on placebo. The May announcement gave 65.3% for 12 mg, an efficacy-estimand figure.
Heart and Metabolic Measures
Several heart and metabolic measures were key secondary end points, controlled for multiple testing, and all improved significantly compared with placebo.
Physical function, measured with a standard quality-of-life questionnaire (SF-36v2), also improved more with retatrutide than with placebo. These are changes in risk markers, not outcomes such as heart attacks or strokes, which TRIUMPH-1 was not designed to measure.
Knee Osteoarthritis and Sleep Apnea Results
In the 574 participants with knee osteoarthritis, knee pain on the WOMAC pain scale fell by 3.5 points with 9 mg and 3.6 points with 12 mg, compared with 1.9 points on placebo.
In the 243 participants with obstructive sleep apnea, the apnea–hypopnea index (breathing interruptions per hour of sleep) fell by 34.3 events per hour with 9 mg and 31.7 with 12 mg, compared with 9.9 on placebo.
These are the figures from the published paper. The company's June 2026 announcement expressed the results as percentages, with reductions of up to 73.1% in knee pain and 60.6% in the apnea–hypopnea index, both with 12 mg and based on the efficacy estimand.
The 104-Week Extension
After 80 weeks, some participants continued for another 24 weeks. The paper says "the first eligible participants (approximately 500 participants)" entered this extension; the May announcement described it as 532 participants with a BMI of 35 or more at the start of the trial. In the extension, participants received retatrutide at the highest dose they tolerated, 9 mg or 12 mg, including those who had been on placebo. The table groups them by their original assignment.
Average weight loss at week 104 in the extension groups was higher than the week-80 figures for the whole trial. Because the extension included only part of the trial population, the two sets of numbers are not directly comparable.
Side Effects in TRIUMPH-1
The most frequent side effects were gastrointestinal. The paper says they "were mostly transient and mild or moderate in severity," and most occurred while the dose was being increased.
A few other findings from the safety data:
- Dysesthesia, an unusual skin sensation such as burning or tingling, was reported by 12.5% of the 12 mg group, compared with 0.9% on placebo; the paper describes these events as mostly mild or moderate and nonserious.
- Low blood pressure was reported by 8.8% of the 12 mg group, compared with 0.9% on placebo, and was more common in people taking blood pressure medicines.
- Stopping because of weight loss: some people stopped treatment because of excessive or sufficient weight loss, 5.3% in the 12 mg group compared with none on placebo.
- Pancreatitis: 8 confirmed cases on retatrutide and 2 on placebo; the authors say these small numbers "do not permit conclusions regarding a treatment effect."
- Deaths: 4 on retatrutide (none on 4 mg, 3 on 9 mg, 1 on 12 mg) and 2 on placebo.
The May announcement gave slightly different discontinuation figures (4.1%, 6.9% and 11.3%, compared with 4.9% on placebo); the table uses the published paper.
What TRIUMPH-1 Does Not Tell Us
- How retatrutide compares with tirzepatide. TRIUMPH-1 compared retatrutide only with placebo. A separate trial, TRIUMPH-5, compares it with tirzepatide.
- What happens after stopping. TRIUMPH-1 did not test stopping the drug (see weight regain after stopping retatrutide). TRIUMPH-6 is studying maintenance of weight reduction.
- Heart and kidney outcomes such as heart attacks and strokes. These are being studied in TRIUMPH-Outcomes, in people with obesity and cardiovascular or kidney disease.
- Results in people with diabetes. TRIUMPH-1 excluded them; TRIUMPH-2 studied people with type 2 diabetes.
What Happens Next
Lilly says it plans to submit a Biologics License Application for retatrutide to the US Food and Drug Administration in the first quarter of 2027. Retatrutide is not approved anywhere, and the FDA will decide on approval after reviewing the full data from the TRIUMPH program.
Sources
- Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169.
- Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
- Eli Lilly. Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications. June 6, 2026.
- Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
- Lilly Trials. The Effect of Retatrutide Once Weekly on Cardiovascular Outcomes and Kidney Outcomes in Adults Living With Obesity (TRIUMPH-Outcomes). NCT06383390, trial listing.
Medical Disclaimer: This article summarizes published clinical trial results for general information only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. Nothing here is a recommendation to use, seek out or avoid any medication.
Frequently asked questions
At 80 weeks, retatrutide 12 mg reduced body weight by 25.0% on average counting everyone randomized, compared with 3.9% on placebo, or by 28.3% compared with 2.2% if everyone had stayed on treatment as intended. The 4 mg and 9 mg doses also reduced weight significantly, and all primary and key secondary end points were met.
TRIUMPH-1 randomized 2,339 adults with obesity, or overweight with a weight-related condition, and without diabetes, at 131 sites in 11 countries. They were assigned in equal numbers to retatrutide 4 mg, 9 mg or 12 mg, or placebo, for 80 weeks.
About 500 participants continued for another 24 weeks. At week 104, those originally assigned to 12 mg had lost 29.9% of their weight counting everyone in the extension, or 30.3% if taken as intended. Lilly described the extension as 532 participants with a BMI of 35 or more at the start.
The most common were nausea, diarrhea, constipation and vomiting, mostly mild or moderate and mostly while the dose was being increased. With 12 mg, 42.4% reported nausea compared with 14.8% on placebo, and 11.2% stopped treatment because of an adverse event compared with 4.6% on placebo.
