Retatrutide Phase 3 Results: TRIUMPH-1 Explained

What is TRIUMPH-1?

Phase 3 is the last and largest stage of testing before a company asks the FDA to approve a drug. TRIUMPH-1 was randomized (a computer chose each person's group), double-blind (neither participants nor study doctors knew who got what) and placebo-controlled (one group got an injection with no active drug, for comparison).

The trial started in July 2023 and finished its main data collection in April 2026. The New England Journal of Medicine (NEJM) published the full results on September 29, 2026, after outside experts reviewed the study.

Who took part

Adults could join with a body mass index (BMI) of 30 or higher, or 27 or higher plus high blood pressure, high cholesterol, sleep apnea or heart disease. People with diabetes could not join. Two smaller studies ran inside the trial: 574 people with knee osteoarthritis and 243 with moderate to severe obstructive sleep apnea.

The four trial arms

People were split evenly into four arms, or groups: retatrutide 4 mg, 9 mg or 12 mg once a week, or placebo. Everyone on retatrutide started at 2 mg, and the trial raised the dose every four weeks until each arm reached its target. These were research doses, not a schedule to follow. The retatrutide trial dose page shows them.

The main trial lasted 80 weeks. A planned extension followed 532 people with a BMI of 35 or higher to week 104. Only people who finished week 80 and tolerated their dose could join it.

What the trial measured

An endpoint is the result a trial is built to measure. The 80-week trial had three primary (main) endpoints: percent change in body weight at 80 weeks on 9 mg and 12 mg versus placebo; knee pain in the osteoarthritis group; and the apnea-hypopnea index (AHI), the number of breathing pauses or shallow breaths per hour of sleep, in the sleep apnea group. Secondary endpoints included waist size, blood pressure and cholesterol.

TRIUMPH-1 results

Average percent of body weight lost at 80 weeks. These are group averages, not what any one person can expect.

In the NEJM paper, knee pain scores fell 3.6 points on 12 mg versus 1.9 on placebo. In people with sleep apnea, breathing events fell by about 32 per hour on 12 mg versus about 10 on placebo.

Lilly said in its press release that 45.3% of people on 12 mg lost 30% or more of their weight. It also said people on 12 mg in the extension lost 30.3% at 104 weeks. That group only included people who stayed on the drug, so it isn’t comparable to the full trial.

Why are there two different numbers?

Both numbers come from the same trial and the same people. They answer different questions.

Each analysis has an estimand: an exact statement of the question it answers. A key part is how it handles changes partway through, such as a person stopping the drug or starting another weight-loss treatment. FDA guidance calls these “intercurrent events.”

• Treatment-regimen estimand (25.0% on 12 mg): this counts everyone who was randomized, whether or not they kept taking the drug. It asks: what happens, on average, to people who start this treatment? The NEJM paper leads with this number.
• Efficacy estimand (28.3% on 12 mg): Lilly defines this as the effect “had all randomized participants remained on study intervention.” It asks: what does the drug do when people keep taking it? Lilly's press release led with this number.

Including people who stopped the drug pulls the 12 mg average down, from 28.3% to 25.0%. The placebo number moves the other way, from 2.2% to 3.9%. One likely reason is that the treatment-regimen method also counts people who started other weight-loss treatments during the trial.

Neither number is wrong. Before comparing retatrutide results, it helps to check which method each uses.

Phase 2 vs phase 3: how do the results compare?

Phase 2 trials are smaller and help choose doses for phase 3. Retatrutide's phase 2 obesity trial came out in 2023.

These are separate trials with different designs, so a side-by-side view is only a rough guide.

The phase 2 results posted on ClinicalTrials.gov say the weight analysis left out data from after people stopped the drug. That makes 24.2% closer in type to Lilly's 28.3% than to NEJM's 25.0%. TRIUMPH-1 also ran 32 weeks longer and enrolled about seven times as many people.

When might retatrutide be FDA approved?

As of September 2026, retatrutide is investigational and not FDA-approved. The FDA says it cannot be used in compounding under federal law.

Lilly said in a July 2026 press release that it plans to submit a Biologics License Application (BLA), the formal request for FDA permission to sell a product, in the first quarter of 2027. It repeated that plan on September 29, 2026.

How FDA review works

1. The FDA checks whether the application is complete enough to review. If not, it can refuse to file it.
2. Within 60 days, the FDA says whether review will be standard or priority. Priority review is for drugs that could be a significant improvement for a serious condition.
3. FDA experts study the data and inspect trial sites. They may ask an outside advisory committee for advice.
4. The FDA approves the drug or explains what is missing.

Under the current user-fee agreement, the FDA aims to act on a new drug or biologic within 10 months of the 60-day filing date for standard review, or 6 months for priority review. A major change to the application during review can add 3 months.

This is our arithmetic from the FDA's goals, not a date from Lilly or the FDA. Goals are targets, and approval is not guaranteed. For the latest status, see Retatrutide Watch.

Side effects in TRIUMPH-1

In the NEJM paper, stomach and gut effects were most common. Lilly said in its press release that on 12 mg, 42.4% had nausea (placebo 14.8%) and 12.5% had dysesthesia, an unusual skin feeling such as tingling (placebo 0.9%). Also, 11.3% on 12 mg stopped because of side effects, versus 4.9% on placebo. See retatrutide side effects for more.