Lilly's retatrutide produced 28.3% average weight loss at highest dose in Phase 3 trial

Eli Lilly reported on May 21, 2026 that retatrutide, an investigational once-weekly injection, produced an average weight loss of 28.3% over 80 weeks at the highest dose tested in a Phase 3 trial called TRIUMPH-1 ^[1]. That equals about 70.3 pounds for a group whose average starting weight was 248.5 pounds and average starting body mass index (BMI) was 40.0 ^[1].

That 28.3% figure uses the trial's "efficacy estimand," a statistical measure that estimates what would have happened if every randomized participant had stayed on treatment ^[1]. On the "treatment-regimen estimand," which averages results regardless of whether people stayed on the drug or started other weight-management treatments, the 12 mg group lost 25.0% on average ^[1].

The numbers by dose

• 4 mg: 19.0% average weight loss, or 47.2 pounds ^[1]
• 9 mg: 25.9%, or 64.4 pounds ^[1]
• 12 mg: 28.3%, or 70.3 pounds ^[1]
• Placebo: 2.2%, or 5.5 pounds ^[1]

In the 12 mg group, 45.3% of participants lost at least 30% of their body weight, compared with 0.5% on placebo ^[1]. About 62.5% lost at least 25%, and 27.2% lost at least 35% ^[1]. Lilly said 65.3% of people on 12 mg reached a BMI below 30, the threshold for obesity, including 37.5% of those who started with class 3 obesity, defined as a BMI of 40 or higher ^[1]. Waist circumference fell by 24.1 centimeters (about 9.5 inches) at 12 mg, versus 3.6 centimeters on placebo, and Lilly reported improvements in non-HDL cholesterol, triglycerides, systolic blood pressure and high-sensitivity C-reactive protein ^[1].

In a pre-specified extension, 532 participants with a starting BMI of 35 or higher who completed the 80-week study went on to 104 weeks of treatment. Those on 12 mg lost an average of 30.3%, or 85.0 pounds, from their original starting weight ^[1]. That extension enrolled only people who finished the main study and tolerated their assigned dose, so it does not represent everyone who starts the drug ^[1].

The trial randomized 2,339 participants ^[1]. CNBC described the study as having roughly 2,500 patients ^[4]. The reason for the difference has not been explained.

Side effects and dropout

The most common side effects at 12 mg were nausea (42.4%), diarrhea (32.0%), constipation (26.1%) and vomiting (25.3%), compared with 14.8%, 13.5%, 10.9% and 4.8% on placebo ^[1]. Dysesthesia, an unpleasant nerve sensation, was reported in 12.5% of the 12 mg group and 12.3% at 9 mg, versus 0.9% on placebo; Lilly said these events were generally mild to moderate, most resolved during treatment, and most participants stayed on the drug ^[1]. Urinary tract infections occurred in 8.4% at 12 mg versus 5.3% on placebo ^[1].

Discontinuation because of adverse events was 11.3% at 12 mg, 6.9% at 9 mg and 4.1% at 4 mg, compared with 4.9% on placebo ^[1]. The 4 mg dose is reached with a single escalation step ^[1]. Lilly's chief scientific and product officer, Dan Skovronsky, told CNBC that 30% weight loss is an "incredible number to see" and that the 4 mg tolerability "exceeded Lilly's expectations" ^[4]. He also said, "For some patients, 30% weight loss may be more than what they're seeking" ^[4]. CNBC reported that Lilly observed no cardiac or liver issues ^[4].

No head-to-head results against tirzepatide, the ingredient in Zepbound and Mounjaro, have been released. CNBC reported that analysts expected retatrutide to beat Zepbound's weight loss of roughly 20% to 22% ^[4]. A separate registered trial, NCT06662383, is designed to compare retatrutide with tirzepatide directly, but no results are posted ^[2].

Why it matters for patients

Retatrutide is not approved for any use and is legally available only to people enrolled in Lilly's clinical trials ^[1]. That means the results do not change what is currently available: semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound) and orforglipron (Foundayo) remain the approved options. Retatrutide works differently, targeting GIP, GLP-1 and glucagon, while tirzepatide targets GIP and GLP-1 and semaglutide targets GLP-1 only ^[1][4].

For people who have struggled with side effects on existing drugs, the 4 mg result may be the more relevant part of the announcement: nearly 20% average weight loss with one dose step and a dropout rate below placebo ^[1]. The high-dose data also show the tradeoff clearly, since more than one in ten people on 12 mg stopped because of side effects ^[1]. Longer-term safety beyond 104 weeks, pricing, and how retatrutide would compare with approved drugs in everyday use have not been disclosed.

What happens next

More TRIUMPH-1 details will be presented at the 86th annual American Diabetes Association Scientific Sessions, with further results at later medical meetings and in peer-reviewed journals ^[1]. Lilly said results from TRIUMPH-2, which studies retatrutide in adults with obesity or overweight and type 2 diabetes, and TRIUMPH-3, in adults with obesity or overweight and established cardiovascular disease, will be shared later in 2026 ^[1]. The broader TRIUMPH program has enrolled more than 5,800 participants since it began in 2023, with more results expected over the next year ^[1]. Lilly has not disclosed when it plans to file for FDA approval.