Retatrutide took 25% off body weight at its top dose

Twelve milligrams of retatrutide, injected weekly for 80 weeks, produced an average weight loss of 25.0% in adults with obesity but without diabetes, against 3.9% on placebo. The figure comes from the treatment-regimen analysis of Eli Lilly’s TRIUMPH-1 phase 3 trial, which randomized 2,339 people across three doses and a placebo arm. It describes the top dose only, since the 4 mg and 9 mg groups finished lower.

A second analysis from the same trial puts the 12 mg arm at 28.3%.

Three doses under two analyses

Retatrutide is a triple agonist, acting on the GIP, GLP-1 and glucagon receptors, and TRIUMPH-1 is its first phase 3 obesity study. Enrollment covered adults with a body mass index of 30 or higher, or 27 or higher with a weight-related condition, and excluded anyone with diabetes. Subgroups included people with knee osteoarthritis or obstructive sleep apnea. Jastreboff, who directs the Yale Obesity Research Center, presented the data at the American Diabetes Association’s Scientific Sessions in New Orleans in June 2026, and the New England Journal of Medicine paper followed.

TRIUMPH-1 split participants 1:1:1:1 between 4 mg, 9 mg, 12 mg and placebo. In Lilly’s May 21, 2026 release, the efficacy estimand, which models outcomes as if everyone stayed on treatment as intended, shows 19.0% at 4 mg, 25.9% at 9 mg and 28.3% at 12 mg, with placebo at 2.2%. The treatment-regimen estimand, which counts people who stopped the drug or took other weight-loss therapy, is the more conservative reading, and American Pharmaceutical Review’s tabulation lists it at 17.6%, 23.7% and 25.0% with placebo at 3.9%.

Both sets of numbers belong to week 80, the trial’s primary timepoint, so the gap between 25.0% and 28.3% reflects how dropouts and rescue therapy are handled rather than a difference in follow-up time or dose. At that mark the 12 mg group lost about 62 pounds on average under the treatment-regimen analysis and about 70 pounds under the efficacy analysis.

ScienceAlert’s account of the New England Journal of Medicine paper leads with the 25 percent number, and that choice is defensible: it is the figure that holds up when dropouts are kept in the denominator. Yale’s Ania Jastreboff, the trial’s lead author, said in Lilly’s release: “Retatrutide may potentially be a highly impactful future tool to treat their obesity and transform their health trajectory.”

The 104-week extension at 12 mg

A smaller extension followed 532 participants with a body mass index of 35 or higher. Under the treatment-regimen analysis, the 12 mg group reached 29.9% average weight loss at 104 weeks. That number belongs to a prespecified subset, not the full randomized population, and it should not be read as the trial-wide result; the 25.0% at week 80 remains the figure that describes everyone randomized to the top dose.

The 104-week treatment-regimen figures in American Pharmaceutical Review’s tabulation climb across the board: 25.7% at 4 mg, 28.7% at 9 mg and 29.9% at 12 mg. The curve flattens at the upper end, with 9 mg and 12 mg separated by 1.2 points after two years, compared with 1.3 points at week 80. Whether the top dose’s extra gastrointestinal burden buys enough additional loss is a judgment the data lay out but do not settle.

Jastreboff said all doses produced meaningful weight reduction for nearly all participants, and that those with severe obesity on the highest dose “lost on average 30% of body weight over two years.” The American Diabetes Association’s release for the trial adds that 65.3% of participants on 12 mg ended with a body mass index under 30.

Tolerability at the 12 mg dose

The same arm carried the heaviest side-effect load. HCPLive’s summary of the ADA presentation gives nausea at 42.4% versus 14.8% on placebo, diarrhea at 32.0% versus 13.5%, constipation at 26.1% versus 10.9% and vomiting at 25.3% versus 4.8%. Dysesthesia, an abnormal skin sensation, appeared in 12.5% of the 12 mg group and 0.9% of placebo.

Lilly reports that 11.3% of 12 mg participants stopped treatment because of adverse events, compared with 4.9% on placebo, rising from 4.1% at 4 mg and 6.9% at 9 mg. ScienceAlert cites roughly 11% against 4.6%, a small difference in the placebo figure between the two accounts. It also reports serious adverse events in 10.5% of the top-dose group versus 5.5% on placebo. TRIUMPH-1 excluded people with diabetes and was funded by Lilly.

Subtracting placebo’s 3.9% from the 12 mg arm’s 25.0% leaves a 21.1-point gap at week 80 under the treatment-regimen analysis, the difference between the top-dose arm and the comparison group.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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