Semaglutide (Ozempic/Wegovy) dramatically improves fatty liver disease

The good news keeps piling up for GLP-1 medications

TL;DR: New clinical trial data shows semaglutide may reverse fatty (non-acoholic) liver disease.

Liver Damage: It’s Not Just the Booze

While you might associate liver disease and cirrhosis with heavy drinking, unfortunately, liver disease from non-alcoholic causes has risen dramatically over the past few decades. Why? The obesity epidemic has driven a rise in “fatty liver” (not to be mistaken for the expensive kind from ducks served in fancy restaurants).

Fatty liver (also called steatosis) can occur with inflammation that damages liver cells and ultimately cause scarring and cirrhosis, which can lead to liver failure, liver cancer, and death.

Source: British Liver Trust

Non-alcoholic fatty liver disease (NAFLD) affects an estimated 27% of Americans and 20% of people in the UK, where cirrhosis due to NAFLD is a common reason for needing a liver transplant. Obesity and type II diabetes are risk factors for fatty liver disease, but it can also occur in lean people who have other metabolic risks such as high cholesterol.

Note: While fatty liver disease has recently been renamed metabolic dysfunction-associated steatotic liver disease (MASLD), in the spirit of plain language communication, I’m going to stick with the previous terminology here. (AI rendering of fatty liver above)

Enter GLP-1 medications

Unless you’ve been living under a rock, you probably know that the new class of drugs called GLP-1 agonists have shown impressive results in clinical trials for diabetes, weight-loss, and even cardiovascular disease and mortality. New results from a randomized clinical trial of semaglutide (brand name Ozempic/ Wegovy) published last week in the New England Journal of Medicine show impressive results for non-alcoholic fatty liver disease as well.

The trial included around 800 people who already had advanced fatty liver disease including signs of liver damage and inflammation. Since the focus was on non-alcoholic fatty liver disease, people with other types of liver disease were excluded, as well as people whose average alcohol intake was more than one drink a day. Baseline liver data were gathered on all participants, and they were followed for 72 weeks after randomization to receive either semaglutide or a placebo.

Since all participants already had evidence of liver damage, the trial measured whether participants saw improvements during the trial. To measure these changes, the researchers looked directly at liver cells that were taken from liver biopsies (as a non-clinician this sounded invasive to me, but apparently it can be done with a needle!).

“Steatohepatitis” is fatty liver with inflammation, and “fibrosis” is the formation of scar tissue in the liver. The trial found that almost 63% of those taking semaglutide had a reduction in liver inflammation, compared to 34% in the placebo group. A significant difference between the groups was also seen for a reduction in fibrosis or liver scarring.

Source: Figure 1, Sanyal, et al, 2025. Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis, New England Journal of Medicine

Consistent with previous trials, the semaglutide group also lost more body weight and had significant improvements in blood pressure, blood glucose, lipids, and inflammation compared to the placebo group. The benefits of semaglutide were similar in participants who did not have type 2 diabetes or obesity at baseline, suggesting that there may be direct effects of the medication on liver health (such as on inflammation) and not only through weight loss. The semaglutide group did have more reported GI complaints, such as nausea and diarrhea, but there was no difference in serious adverse events (and more deaths in the placebo group). This particular clinical trial is still ongoing, and will follow people up to 240 weeks to test whether the drug can prevent liver cirrhosis.

As a scientist following the GLP-1 data with great interest, I was excited to see this study. The evidence for wide-ranging benefits of GLP-1 drugs beyond diabetes continues to mount. The liver has enormous capacity for healing and regeneration when the source of damage is removed (keep this in mind if you are thinking of reducing your alcohol intake!). While lifestyle changes that lower metabolic risk can also improve fatty liver disease, having an effective medication would be huge. For me it would be interesting to see if GLP-1s can reduce inflammation and liver damage in other types of liver disease, including fatty liver from a combination of metabolic risk and alcohol consumption (I’m guessing a decent fraction of Americans and Britons with fatty liver fall have both of these risk factors).

With more clinical trials for different outcomes, treatment indications for GLP-1 medications could eventually be expanded beyond their current approvals for diabetes and weight loss….stay tuned!

Stay well,

Jenn

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