Healthcare (Commonwealth Union) – The liver has a key role as a central processing unit for the body. It changes nutrients from food into energy that can be utilized, stores vitamins and minerals, and has a role in regulating blood sugar levels. As we consume food, everything absorbed from the digestive system moves via the liver, where it is kept, changed, and distributed. In the absence of this procedure, we would have a hard time in maintaining stable energy and metabolic function.
Researchers have noted that semaglutide—the vital component in widely used weight-loss drugs that replicate the GLP-1 gut hormone—directly targets a specific group of liver cells to enhance their function, and it does so without relying on weight loss.
Repurposing existing medicines as been a key focus due to the fact that they have already been tested safety purposes.
This breakthrough overturns long-standing beliefs about how GLP-1 medications like Ozempic and Wegovy affect the liver, and it may lead to new approaches in treating metabolic liver disease, which is expected to impact nearly two billion people globally by 2050.
For years, researchers have been uncertain about how semaglutide benefits the liver. While the drug is known to reduce blood sugar levels and support weight loss, improvements in liver health have been observed that cannot be fully explained by these effects alone.
Daniel Drucker, who is a senior investigator at the Lunenfeld-Tanenbaum Research Institute at Sinai Health and a University Professor of endocrinology and metabolism at the University of Toronto, Temerty Faculty of Medicine who led the study says “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.”
Daniel Drucker has been a leading figure in GLP-1 research since the 1980s, when his early breakthroughs helped establish the foundation for today’s GLP-1–based therapies.
Following their success in treating type 2 diabetes and obesity, semaglutide and similar GLP-1 drugs have since been approved for additional conditions, including metabolic dysfunction–associated steatohepatitis (MASH). This serious form of fatty liver disease involves fat accumulation, inflammation, and scarring, which can progress to cirrhosis and liver failure. It affects roughly a quarter of Canadian adults and is strongly associated with obesity and type 2 diabetes, with treatment often focusing on weight reduction through lifestyle changes.
Now, Drucker and his colleagues have shown that semaglutide directly targets the liver, helping to reduce inflammation and fibrosis while improving overall function—independently of any weight loss. Their findings, published in Cell Metabolism, challenge a long-standing belief that liver cells lack the receptor needed for semaglutide to act, suggesting the drug does in fact have a direct pathway to influence the organ.
The results have important real-world implications. While GLP-1 medicines are now widely prescribed, their effects beyond appetite control and blood sugar regulation are not yet fully understood. Evidence that semaglutide can enhance liver health independently of weight loss may shape how it is prescribed. Doctors could opt for lower doses that minimise the side effects linked to higher, weight-loss-focused dosing, which may also help reduce treatment costs for patients, according to Drucker.
“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.”
The study was supported by funding from the Canadian Institutes of Health Research, along with a grant from the Sinai Health–Novo Nordisk Foundation Fund in Regulatory Peptides.
