Fatty liver disease goes down with novel weight loss drugs, shows new study: What does this mean for therapy?

Clinical trial found semaglutide reduced liver inflammation and scarring

Nearly two in three people with fatty liver disease lost some of the liver fat and inflammation after using semaglutide 2.4 mg weekly shots for one-and-a-half years, according to initial results from an ongoing phase 3 trial, published recently in the New England Journal of Medicine.

Importantly, around one in three patients also saw reduction in liver fibrosis or scarring of the liver that prevents it from functioning properly.

 

Metabolic dysfunction-Associated Steatotic Liver Disease (MAFLD) — until recently referred to as the Non-Alcoholic Fatty Liver Disease — is a chronic condition where there is an excessive build-up of fat on the liver. This fat accumulation leads to inflammation, scarring of the liver and may even cause liver cancer. The prevalence of MAFLD in India is estimated to be between 9% and 32%.

 

Dr SK Sarin, liver specialist and vice-chancellor of the Institute of Liver and Biliary Sciences, talks about the significance of the findings.

 

What do the results of the phase III trial tell us?

This is a very important study, which builds on the findings of the phase 2 trial on the impact of semaglutide on MASLD. Phase 2 trials are usually done to fix the dosing and the highest 2.4 mg dose of the medicine was used for the current trial. The results show that 62.9% of the people on semaglutide saw a loss of liver fat and inflammation as compared to 34.3% among people given placebo. The stiffening of the liver also reduced in 36.8% of the participants on semaglutide as compared to 22.4% on placebo.

The participants lost around 10% of their body weight in the current trial as compared to 14% recorded previously. All in all, the study shows promising results for fatty liver disease.

 

How does the drug work? Are these the effects of weight loss?

Semaglutide belongs to a class of medicines known as GLP-1 receptor agonists which mimic the action of certain gut hormones to improve secretion of insulin, inhibit secretion of glucagon that stimulates glucose production in the liver, and also reduce appetite by slowing down digestion. The study does not look into the confounding variable of weight loss, so we cannot say if there is any other reason for the improvements seen.

 

However, it is well-known that when people lose weight, MASLD improves. People who lose around 7-10% of their body weight, see a reduction in liver fat. And, with a weight-loss of more than 10%, they see regression in fibrosis. This happens even if people lose weight without using these drugs.

 

What is the current treatment for MASLD? What are the challenges?

The best way to treat MASLD is weight loss — be it with drug or with diet and exercise. The drug is meant for people who are not able to move and exercise or are unable to lose weight with diet and exercise. They come with several side effects such as vomiting, nausea, and even serious side effects such as stomach paralysis, inflammation of the pancreas, and thyroid cancer.

At present, there are three lines of treatment. One, of course, are the GLP-1 drugs that work on the gut hormones. Two, a drug called resmetirom that works on the thyroid hormone — this is again very expensive at around $ 5,400 a month. Third, FGF21 medicines that work on the adipose tissues. All of these medicines are meant to help with weight loss and thereby improve the liver.

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