ESSENCE Part 1 shows semaglutide reverses liver inflammation in MASH

Results from part 1 of the phase 3 ESSENCE trial, published April 30, 2025, show that once-weekly semaglutide 2.4 mg improved liver tissue findings in people with metabolic dysfunction-associated steatohepatitis (MASH) and moderate or advanced liver scarring ^[1]. Both of the study's main goals were met.

MASH is a form of fatty liver disease in which fat buildup is accompanied by inflammation and liver cell injury. Over time it can cause fibrosis, or scarring, and progress to cirrhosis. ESSENCE enrolled 1,197 patients with MASH confirmed by biopsy and fibrosis stage 2 or 3, and randomly assigned them in a 2:1 ratio to semaglutide 2.4 mg by weekly injection or placebo for 240 weeks ^[1]. The published results come from a planned interim analysis at week 72 in the first 800 patients, which the investigators call part 1 ^[1].

What the trial measured

The two primary endpoints were resolution of steatohepatitis without worsening of liver fibrosis, and reduction in liver fibrosis without worsening of steatohepatitis — both judged on liver biopsy ^[1].

Steatohepatitis resolved without worsening fibrosis in 62.9% of the 534 patients taking semaglutide, compared with 34.3% of the 266 patients on placebo, an estimated difference of 28.7 percentage points (95% CI, 21.1 to 36.2; P<0.001) ^[1]. Fibrosis improved without worsening steatohepatitis in 36.8% of the semaglutide group versus 22.4% of the placebo group, a difference of 14.4 percentage points (95% CI, 7.5 to 21.3; P<0.001) ^[1].

Among the secondary outcomes included in the statistical testing plan, 32.7% of semaglutide patients achieved both resolution of steatohepatitis and reduction in fibrosis, versus 16.1% on placebo — a 16.5-percentage-point difference (95% CI, 10.2 to 22.8; P<0.001) ^[1]. Mean body weight change was −10.5% with semaglutide and −2.0% with placebo, a difference of 8.5 percentage points (95% CI, −9.6 to −7.4; P<0.001) ^[1]. Mean changes in bodily pain scores did not differ significantly between the two groups ^[1].

On safety, the published abstract reports that gastrointestinal adverse events were more common in the semaglutide group ^[1]. The detailed breakdown of those events, and of any serious adverse events, is not included in the abstract text available here.

Why it matters for patients

MASH has historically had few drug options, and the endpoints used here — biopsy-confirmed resolution of inflammation and improvement in fibrosis — are the measures regulators have used to judge whether a liver drug is working ^[1]. That makes this the first large, randomized, placebo-controlled evidence that a GLP-1 medicine many people already take for weight or diabetes can change liver tissue itself in this population.

A few caveats are built into the design. This is an interim look at 800 of 1,197 enrolled patients at week 72 of a 240-week study, so it does not yet answer whether the liver benefit lasts, or whether it translates into fewer cases of cirrhosis, liver failure, transplant or death ^[1]. Enrollment was limited to people with biopsy-confirmed MASH and fibrosis stage 2 or 3, so the findings do not directly speak to people with milder fatty liver or with cirrhosis ^[1]. The placebo response was substantial — a third of placebo patients also had resolution of steatohepatitis — which is common in liver biopsy trials and is one reason the comparison, rather than the raw percentage, is the number to watch ^[1].

It is also worth noting that participants on semaglutide lost about 10.5% of body weight on average ^[1]. The trial as reported does not separate how much of the liver improvement came from weight loss versus other effects of the drug.

The trial was funded by Novo Nordisk, which makes semaglutide, and is registered as NCT04822181 ^[1].

What happens next

The study is ongoing and is designed to run 240 weeks, with the remaining patients and longer-term outcomes still to be reported ^[1]. Whether and when US regulators act on these data, what the label would say, and how insurers would cover it are not addressed in the published trial report. Readers with liver disease questions can raise these results with the clinician managing their care.