By A.J. Hostetler
A new analysis of a large international clinical trial finds semaglutide, a compound found in weight loss medications Wegovy and Ozempic, reduces major heart events and lowers fatty liver disease risk in adults with both obesity and heart disease.
People with obesity face a higher risk of heart attacks and strokes. Many also have fatty liver disease that can lead to liver scarring. A common liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), affects about 4 out of 10 adults and is closely linked to obesity, type 2 diabetes and high blood pressure.
Researchers at Virginia Commonwealth University and around the world are studying the effects of semaglutide on both heart and liver diseases. VCU hepatologist Arun Sanyal, M.D., and colleagues last year published results from the “Effect of Semaglutide in Subjects with Non-cirrhotic Non-alcoholic Steatohepatitis” (ESSENCE) clinical trial, demonstrating that it improves fatty liver disease and lowers the risk factors associated with heart disease.
Arun Sanyal, M.D., is the director of VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health. (Enterprise Marketing and Communications)
A new analysis of a separate clinical trial, “Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity” (SELECT), shows that semaglutide indeed lowers cardiac risks in those who also have fatty liver disease, even those who have advanced liver scarring. The results were recently published in the journal Nature Medicine; Sebastian M. Meyhöfer of Novo Nordisk Pharma GmbH, in Germany, is the paper’s corresponding author and Sanyal is a co-author.
“This is a landmark study, demonstrating unequivocally the benefits of semaglutide in those at high risk for cardiovascular disease,” said Sanyal, director of VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health.
In this clinical trial, people who injected semaglutide for two years had fewer major heart events, such as heart-related death, heart attack or stroke, than those who got a placebo. And in people with higher scores on a non-invasive measure for liver scarring, called the FIB-4, semaglutide lowered major heart events by about 26%.
Semaglutide also led to a much larger improvement in the fatty liver index, a blood-based measure of liver fat, of about a 28% greater decrease than placebo.
“In this analysis, we show that these benefits are also seen in those with non-invasive markers for MASLD and liver scarring, including advanced fibrosis. These, together with the data from ESSENCE, provide a strong rational to consider semaglutide in those with MASLD even with advanced fibrosis for its liver and cardiometabolic benefits,” Sanyal said.
Fatty liver disease occurs when fat builds up in the liver, leading to inflammation and scarring. Over time, it can lead to cirrhosis and even liver failure that requires a liver transplant as well as heart disease, making it a major public health concern.
Semaglutide, manufactured by Novo Nordisk, belongs to a class of drugs called GLP-1 receptor agonists. As Wegovy and Ozempic, it is approved by the U.S. Food and Drug Administration for different conditions, including diabetes and obesity. Only Wegovy is FDA-approved to reduce cardiovascular disease risks for patients with certain medical conditions. Sanyal, a leading researcher of semaglutide in liver patients, consults for and has received grants from Novo Nordisk.
The SELECT clinical trial was an international study conducted at 804 clinical sites across 41 countries, involving over 17,000 patients.
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