Researchers at Sinai Health in Toronto announced on Apr. 15 that semaglutide, a drug used for weight loss and diabetes, directly improves liver function independent of weight reduction. The study, published in Cell Metabolism, found that the drug acts on specific liver cells to reduce inflammation and scarring.
This finding challenges previous beliefs about how GLP-1 medicines like semaglutide work. It could change how doctors treat metabolic liver disease, as these drugs were previously thought to benefit the liver only through their effects on blood sugar and body weight.
Dr. Daniel Drucker has been leading research into GLP-1 since the 1980s. He said, "It turns out that the receptor responsible for these benefits is in a very specialized population of liver cells. And this receptor orchestrates the production of molecules that talk to many different types of liver cells to calm down the inflammatory environment that is the problem in metabolic disease." Dr. Drucker is also a University Professor of medicine at the University of Toronto.
The study focused on MASH (metabolic dysfunction-associated steatohepatitis), a severe form of fatty liver disease affecting about one quarter of Canadian adults. Postdoctoral fellow Dr. Maria Gonzalez-Rellan led research using mouse models and molecular analysis to show that semaglutide's effects are linked specifically to receptors found in certain endothelial and immune cells within the liver.
Further experiments showed mice lacking these key receptors did not see improvements from semaglutide even after losing significant body weight, while others experienced benefits without any associated weight loss.
Dr. Drucker said this discovery may influence prescribing decisions: "We're not saying weight loss isn't important because many things improve when patients lose weight. But we now know that weight shouldn't be the only measure of success, because GLP1 medicines will improve liver health whether or not the patient loses weight." He suggested lower doses could be considered for some patients, potentially reducing side effects and costs.
