Weight-loss jabs could improve liver health by reducing inflammation and scarring even without significant weight loss, a new study has found.
Researchers at Toronto's Sinai Health have found that semaglutide, the active ingredient in popular weight-loss drugs that mimic the gut hormone GLP-1, can act directly on a type of liver cell.
Semaglutide, sold under the brand names Wegovy and Ozempic, is currently used for weight loss and type 2 diabetes, but has been shown to help treat metabolic dysfunction-associated steatohepatitis (MASH) – a long-lasting liver condition caused by having too much fat in the liver.
The severe form of fatty liver disease, which affects about 3 million people in the UK, can improve with weight loss. But researchers have said weight-loss jabs also improve patients' livers in ways that losing weight alone could not.
Dr Daniel Drucker, a senior investigator at the Lunenfeld-Tanenbaum Research Institute, said: “We’ve seen in clinical trials that patients who lose very little weight see the same reductions in liver inflammation, scarring and enzyme levels as those who lose a great deal of weight. Now we know why.”
The findings, published in the journal Cell Metabolism, went against the assumption that liver cells do not carry the receptor that semaglutide binds to, meaning the drug had no direct route to have any impact on the organ.
Dr Maria Gonzalez-Rellan studied mouse models of MASH and molecular analyses of liver cells and found two cell types carrying semaglutide receptors: liver sinusoidal endothelial cells (LSECs) and immune T cells.
She found that semaglutide reversed MASH in mice that lacked the brain receptors controlling appetite, suggesting that weight loss is not required for liver benefits. In a further test, mice lacking LSEC receptors showed no liver improvement on semaglutide even after losing 20 per cent of their body weight.
Analysis revealed semaglutide shifts gene activity in LSECs and makes them release anti-inflammatory molecules, helping the liver become healthier.
Knowing that semaglutide improves liver health independently of weight loss could influence prescribing decisions. Doctors may choose lower doses that avoid the side effects associated with the higher doses needed for significant weight loss, potentially also lowering costs for patients, said Dr Drucker.
He added: “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 GLP-1 medicines will improve liver health whether or not the patient loses weight.”
Naveed Sattar, professor of cardiometabolic medicine at the University of Glasgow, believes most of the benefits of semaglutide are from weight loss itself, but welcomes this “pleasant surprise”.
“While weight reduction clearly leads to marked declines in liver fat, these drugs may also have important direct effects on liver biology. If confirmed, this would represent yet another pleasant surprise with these medicines,” he told The Independent.
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