Retatrutide trial results so far: what phases 2 and 3 show

Retatrutide, a single molecule that activates the GIP, GLP-1 and glucagon receptors, has reported the largest mean weight changes of any compound we have verified for this site: -24.2% at 48 weeks in a phase 2 trial published in the New England Journal of Medicine, and -28.3% at 80 weeks in the highest arm of TRIUMPH-1, a phase 3 trial reported by its sponsor in May 2026. The same record also shows dose-related side effects that matter. This article lays out what each trial found, how strong each source is, and what is still unknown.

What does retatrutide target?

Retatrutide is an agonist of three receptors: glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. Its closest relative on this site is tirzepatide, which activates the first two. The glucagon receptor is what retatrutide adds. Why that addition changes the outcome, and by how much, is an open research question that the trial results alone do not answer.

What did the phase 2 trial find?

The phase 2 trial, led by Ania Jastreboff and published in 2023, was double-blind and placebo-controlled. It enrolled 338 adults with obesity, or overweight plus at least one weight-related condition, and ran for 48 weeks. The primary endpoint was percent change in body weight at 24 weeks. At that point the groups had lost 7.2% (lowest arm), 12.9%, 17.3% and 17.5% (highest arm) versus 1.6% on placebo.

At 48 weeks the figures were 8.7%, 17.1%, 22.8% and 24.2% for the four retatrutide groups versus 2.1% on placebo. In the highest arm, 100% of participants lost at least 5% of body weight, 93% lost at least 10%, and 83% lost at least 15%, against 27%, 9% and 2% on placebo. Gastrointestinal events were the most common adverse events, were related to dose, and were partly reduced when the trial used a lower starting dose. Heart rate rose in a dose-dependent way, peaked at 24 weeks, and declined afterward.

What did the phase 3 readouts add?

TRIUMPH-1 randomized 2,339 participants in equal groups to three retatrutide arms or placebo, with a primary analysis at 80 weeks and a blinded extension to 104 weeks. At 80 weeks the three arms lost 19.0%, 25.9% and 28.3% of body weight versus 2.2% on placebo. In a subgroup with a baseline BMI of at least 35 who continued into the extension, reported weight loss reached 30.3% at 104 weeks.

TRIUMPH-4 studied 445 adults with obesity or overweight and knee osteoarthritis for 68 weeks. The two retatrutide arms lost 26.4% and 28.7% versus 2.1% on placebo. Knee pain scores on the WOMAC scale fell by 4.5 and 4.4 points in the retatrutide arms and by 2.4 points on placebo.

What are the safety signals?

Discontinuation because of adverse events in TRIUMPH-1 was 4.1%, 6.9% and 11.3% across the three arms versus 4.9% on placebo. Dysesthesia, an abnormal sensation of the skin, occurred in 5.1%, 12.3% and 12.5% of the arms versus 0.9% on placebo.

TRIUMPH-4 showed the same pattern at higher rates. Dysesthesia occurred in 8.8% and 20.9% of the two retatrutide arms versus 0.7% on placebo, and adverse-event discontinuation was 12.2% and 18.2% versus 4.0%. We did not find an explanation for the dysesthesia signal in the sources we opened, and long-term safety beyond roughly two years is unreported.

How should the numbers be compared with tirzepatide?

Tirzepatide's pivotal trial, SURMOUNT-1, reported -20.9% at 72 weeks in its highest arm versus -3.1% on placebo. Setting that beside retatrutide's -28.3% at 80 weeks invites the conclusion that retatrutide works better. The comparison does not support that conclusion. The trials differ in length, population, analysis method and sponsor reporting, and no randomized head-to-head trial of the two has been reported in the sources we opened. For a trial that did compare two approved molecules directly, see our semaglutide versus tirzepatide breakdown, and for the wider evidence ranking see our comparison of weight-loss peptides by trial data.

What is retatrutide's status, and what does that mean for research material?

None of the sources we opened, checked on October 6, 2026, reports an approval of retatrutide by the FDA or another regulator. Reports describe a planned regulatory submission, and outlets differ on its timing, so we do not state one. The TRIUMPH figures above come from sponsor announcements relayed by trade press. We did not find the peer-reviewed phase 3 papers yet, and sponsor-reported topline data can change once full analyses appear.

Retatrutide sold as a research chemical is not the trial drug. It was not made, tested or labeled to a pharmaceutical standard, and the FDA's page on unapproved GLP-1 drugs, dated October 1, 2026, warns about products labeled for research purposes that are sold for human use. Core Power Peptides does not stock retatrutide, as our profile notes. Anyone looking for weight management should speak to a physician about approved options.

Bottom line

Retatrutide has the strongest weight-change results we have verified, backed by one peer-reviewed phase 2 trial and two sponsor-reported phase 3 readouts. It also has the clearest dose-related safety signals in this group, led by dysesthesia and discontinuation. The open questions are peer-reviewed phase 3 data, long-term safety and regulatory outcome. Our retatrutide profile tracks the status, and the price comparison table covers the compounds Core Power Peptides does stock.