Novo semaglutide data show liver fat normalised in 88% of obese adults

Novo Nordisk has presented post hoc data from a sub-population of its STEP UP obesity trial showing that semaglutide, marketed as Wegovy, drove substantial reductions in liver fat over 72 weeks in adults with obesity who had no diabetes. The analysis was shared at the European Association for the Study of Diabetes Annual Meeting 2026 in Milan.

Among the 55 participants whose liver fat was directly quantified by MRI-proton density fat fraction, mean hepatic fat fell from 8.8% at baseline to 3.1% by week 72. Of the 26 participants who entered the study with liver fat above the 5% threshold that defines hepatic steatosis, 23 (88.5%) reached normal levels by the end of the study period.

The data in context

The pooled analysis drew from 1,919 adults across the STEP UP and STEP UP T2D trials, of whom more than 94% were classified at high risk for fatty liver at baseline using the Fatty Liver Index. Fewer than 1% met criteria for advanced fibrosis risk, meaning the cohort represented a population with metabolic burden but relatively early-stage liver involvement. The liver-fat substudy was an exploratory post hoc analysis and was not a pre-specified endpoint of either parent trial, a distinction that limits the statistical weight of the findings relative to a dedicated liver study.

Eric Lawitz, of the Texas Liver Institute and University of Texas Health San Antonio, said the results suggested semaglutide "may help address liver disease early, before it becomes a serious health problem" affecting the heart, kidneys, liver and metabolic function. He noted that as many as three in four people with obesity may carry excess liver fat, framing the potential public health relevance of the finding.

Competitive and regulatory landscape

The MASH treatment space has become one of the most closely watched in metabolic disease, following the approvals of resmetirom (Madrigal Pharmaceuticals) and, more recently, semaglutide itself for MASH under the Wegovy brand in the United States, Canada, the United Kingdom, China and several other markets. Novo's dedicated ESSENCE Phase 3 trial evaluated semaglutide 2.4 mg in participants with MASH and moderate to advanced fibrosis; Part 1 results demonstrated reversal of liver damage at 72 weeks, and Part 2 data are expected in 2029.

The STEP UP sub-analysis reinforces that signal in a broader, lower-risk obesity population, which could support label discussions and physician messaging around early hepatic benefit. Filip Knop, Novo's chief medical officer, framed the findings as moving attention "beyond the number on the scale" toward the quality of metabolic improvement achieved with semaglutide treatment.

Competitors including Eli Lilly, with tirzepatide, and a number of clinical-stage companies pursuing FGF21 analogues and thyroid hormone receptor-beta agonists are also gathering liver-fat data in obesity and MASH populations. Novo's accumulating dataset across multiple trial programmes gives it a breadth of evidence that will be difficult for newer entrants to match quickly, though the post hoc nature of the STEP UP liver sub-analysis means it is best read as hypothesis-generating rather than confirmatory. Full peer-reviewed publication of the EASD abstract data will be an important next step in establishing the evidence base.