Drugs like Wegovy can be effective at treating fatty liver disease

A popular drug for treating obesity and diabetes is now showing benefits in fighting a deadly liver disease.

Semaglutide, marketed under names including Ozempic and Wegovy, aids weight loss and blood sugar regulation by mimicking a natural hormone, GLP-1, which curbs the appetite and triggers insulin release. Now, researchers have discovered that the medication can also halt – or in some cases even reverse – the condition known as metabolic dysfunction-associated steatohepatitis (MASH).

“This potentially offers a foundational approach to the management of this condition,” says Philip Newsome at King’s College London. “It’s quite exciting for patients.”

“This is just groundbreaking news,” says Jeffrey Lazarus at CUNY School of Public Health & Health Policy in New York, especially in combination with last year’s US Food and Drug Administration approval of a drug for the condition, resmetirom. “We’ve had no treatment for this disease apart from non-pharmaceutical interventions, like approved diet and physical activity. And now with both these drugs, there’s finally something more we can do.” Even so, the medications should never replace lifestyle changes, but complement them, he adds.

MASH, formerly called NASH, is the severe form of non-alcoholic fatty liver disease marked by increased fat build-up in the liver that leads to inflammation and fibrosis – the formation of scar tissue – and sometimes cirrhosis and cancer. MASH is typically linked to obesity and often to type 2 diabetes.

In a trial in 2020 involving 320 people, Newsome and his colleagues found that a daily semaglutide injection led to reduced liver fat and inflammation in 59 per cent of those with MASH. But a more recent study in 71 patients showed no benefits of a weekly regime.

To get a broader view, Newsome and Arun Sanyal at Virginia Commonwealth University began a bigger trial involving 1195 MASH patients at 253 clinical sites in 37 countries. On average, participants were 56 years old with a body mass index of 34.6. About half had type 2 diabetes.

Doctors prescribed each participant a weekly injection of either semaglutide or a placebo to take for four and a half years. The dose – gradually increasing over the first four months to 2.4 milligrams – corresponds to that used in Wegovy and was chosen based on earlier trial results. Patients were also offered lifestyle counselling to encourage a healthy diet and exercise.

While the full study period is ongoing, after 72 weeks, the researchers analysed the biopsy results of the first 800 patients, including 266 who had placebo injections. They found that 62.9 per cent of those taking semaglutide had marked reductions in liver fat and inflammation, compared with 34.3 per cent of the placebo group. Fibrosis improved for 36.8 per cent of the treated group but only 22.4 per cent of the placebo group. About a third of all treated patients, and 16.1 per cent of the placebo patients, had both these benefits.

Weight loss alone may have contributed to such improvements, as people in the treated group lost an average of 10.5 per cent of their body weight, compared with only 2 per cent of body weight for those taking placebos. But the treatment itself might also directly target the disease-causing process – although more research is needed to fully understand the mechanisms.

“Nothing’s proven yet, but it may well be that part of the effect of GLP-1-like drugs is that they act on immune cells to sort of temper inflammation,” says Newsome.