Tejal Somvanshi
Most coverage of retatrutide centers on the scale, but the most striking figure from Eli Lilly’s TRIUMPH-1 Phase 3 trial concerns the liver. At Week 80, 86 percent of participants with obesity achieved a reduction of at least 30 percent in hepatic steatosis, the fat content of liver tissue, measured by MRI. Many wellness blogs and med-spa websites leave that result out entirely, and some merge TRIUMPH-1 with the separate TRIUMPH-2 study in people with type 2 diabetes. The two trials produced different outcomes, so the distinction matters.
TRIUMPH-1 enrolled 2,539 adults with a body mass index of 30 or higher and no diabetes. Participants receiving retatrutide lost 28.3 percent of their body weight, according to results published in the New England Journal of Medicine. For comparison, tirzepatide, sold as Mounjaro and Zepbound, produced 21.1 percent weight loss at 72 weeks in the SURMOUNT-1 trial. Tirzepatide acts on two hormone receptors, GIP and GLP-1, while retatrutide adds a third target, the glucagon receptor, which is why it is called a triple agonist. The trials differed in design, duration and population, so the numbers are not a direct head-to-head comparison. Retatrutide’s result in the TRIUMPH-2 trial in type 2 diabetes was a separate 20.6 percent weight reduction at 48 weeks and should not be read as part of the TRIUMPH-1 finding.
The liver measurement relied on MRI-PDFF, a magnetic resonance technique that estimates the proportion of fat within liver tissue. The 86 percent figure counts participants who met the 30 percent reduction threshold, which means the remaining participants did not. Lilly reported this liver effect alongside the weight data, and it appears to stand apart from the amount of weight lost. Retatrutide’s glucagon activity offers a plausible explanation, since glucagon signaling influences how the liver processes fat. Lilly summarized the topline findings in an Eli Lilly press release, but longer studies will be needed to confirm whether the liver benefit lasts and whether it reduces liver-related complications.
Eli Lilly plans to file retatrutide with the U.S. Food and Drug Administration in the first quarter of 2027, so a decision is not expected before 2027, and no version of the drug is approved yet. The most common side effects were nausea at 44 percent, vomiting at 28 percent, diarrhea at 23 percent, constipation at 16 percent and redness at the injection site at 12 percent. The trial enrolled adults with obesity who did not have diabetes, and its design is listed in the ClinicalTrials.gov registry. Anyone who sees retatrutide or similar injectables offered outside a licensed pharmacy should review our reporting on compounded injectable sterility alerts first, because unapproved products carry risks that trial results do not address.
How does retatrutide differ from tirzepatide for fat loss? Retatrutide adds glucagon receptor activation to the GIP and GLP-1 pathways that tirzepatide already targets. In TRIUMPH-1, retatrutide produced 28.3 percent weight loss, while tirzepatide reached 21.1 percent in SURMOUNT-1, and retatrutide also reduced liver fat by at least 30 percent in 86 percent of participants. Because the studies differ in design, these numbers point to a difference in mechanism rather than a proven clinical advantage. Readers already taking tirzepatide should also check our coverage of the tirzepatide recall.
The liver fat result has begun to reshape how the obesity drug category is discussed, moving attention from scale numbers toward metabolic health.
