Semaglutide Shows Promise for Fatty Liver Disease

This is a bit of an in-depth read into the promising signs that semaglutide can have a positive impact on those with fatty liver disease or those on the way to having fatty liver disease.


The diabetes medication, alone or in combination regimens, led to improvements in NASH and fibrosis.

Semaglutide, a medication used to treat type 2 diabetes, increased the likelihood of improvement in non-alcoholic steatohepatitis (NASH) without worsening liver fibrosis, according to research presented at the AASLD virtual Liver Meeting. What’s more, combining semaglutide with other drugs led to greater improvements in various measures of fibrosis, metabolism and liver health.


Non-alcoholic fatty liver disease (NAFLD) and its more severe form, NASH, are responsible for a growing burden of advanced liver disease worldwide. Linked to obesity and diabetes, NAFLD and NASH are increasingly recognized as manifestations of metabolic syndrome, a cluster of conditions linked to increased cardiovascular risk. The buildup of fat in the liver triggers cell death and inflammation, which over time can lead to fibrosis, cirrhosis, liver cancer and liver failure.



Developing treatments for NAFLD and NASH has proved challenging. Several drugs that appeared promising in early studies did not show significant benefits in larger clinical trials. With no approved therapies, management currently relies on lifestyle changes, such as weight loss and exercise.


Semaglutide Monotherapy

Philip Newsome, PhD, of Birmingham Biomedical Research Centre in the United Kingdom, presented results from an international Phase II study of semaglutide for people with NASH. The research was also published in The New England Journal of Medicine.


The study enrolled people with biopsy-confirmed NASH, mild to advanced liver fibrosis and a body mass index indicating overweight or obesity. About 60% were women, nearly 80% were white and the mean age was 55. Nearly two thirds had diabetes, and half had advanced fibrosis.


The trial participants were randomly assigned to receive one of three doses of semaglutide (0.1, 0.2 or 0.4 milligrams) or a placebo administered by injection once daily for 72 weeks. Liver biopsies were performed at the start and the end of the study.


Semaglutide (an injectable formulation sold as Ozempic and an oral version sold as Rybelsus) is a glucagon-like peptide-1 (GLP-1) receptor agonist that mimics the action of natural GLP-1, which increases insulin secretion and plays a role in appetite regulation and glucose and lipid metabolism.


The primary study endpoint, assessed in the 230 participants with moderate (Stage F2) or advanced (Stage F3) fibrosis, was NASH resolution with no worsening of fibrosis. Improvement in fibrosis with no worsening of NASH was a secondary endpoint. (Some NASH trials look at these endpoints in the reverse order.)


More participants taking any dose of semaglutide experienced NASH resolution (40%, 36% and 59%, respectively, in the 0.1, 0.2, and 0.4 mg dose groups) compared with the placebo arm (17%).


The proportion of people with fibrosis improvement was statistically similar in all groups: 46%, 32%, 43% and 31%, respectively. However, fewer people taking semaglutide