Novo Nordisk weight-loss drug shows liver benefits in mouse study

A weight-loss drug developed by Novo Nordisk may deliver direct benefits to the liver, according to new preclinical research that challenges existing assumptions about how the medicines work.

Glucagon-like peptide-1, or GLP-1, drugs such as Ozempic and Wegovy have been widely prescribed for diabetes and obesity, with their therapeutic effects largely attributed to weight reduction. However, findings from a mouse study suggest these treatments may also act directly on the liver, independent of their metabolic impact.

Scientists had previously believed that liver cells lacked the receptors targeted by GLP-1 drugs, implying that any observed improvements in liver health were secondary to weight loss. The new research challenges this view, identifying a subset of liver cells that do express these receptors.

In experiments involving mice with fatty liver disease, researchers found that liver sinusoidal endothelial cells, or LSECs, respond directly to semaglutide. Although these cells make up only around 3 per cent of the liver’s cellular composition, they play a critical role in regulating the exchange of substances between the bloodstream and liver tissue.

LSECs line the liver’s network of small blood vessels and are characterised by their porous structure, which enables them to filter molecules passing through the organ. The presence of GLP-1 receptors on these cells suggests a previously unrecognised pathway through which semaglutide may exert protective effects on liver function.

The findings add to growing evidence that GLP-1 therapies could have broader clinical applications, particularly in the treatment of liver diseases such as metabolic dysfunction-associated steatotic liver disease. Further studies in humans will be required to determine whether the mechanisms observed in mice translate to clinical outcomes.