GLP-1s Can Prevent Cirrhosis in People with Fatty Liver Disease

Researchers found that people with diabetes and metabolic dysfunction-associated steatotic liver disease taking glucagon-like peptide 1 receptor agonists (GLP-1RAs) like Ozempic had a slightly lower risk of developing liver complications.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), impacts over 100 million people in the United States. The condition occurs when excess fat builds up in the liver, leading to liver inflammation.

People at higher risk for MASLD include those with obesity, high cholesterol, type 2 diabetes, and other conditions associated with metabolic syndrome.

Moreover, about 25% of people with MASLD develop liver damage, known as non-alcoholic steatohepatitis (NASH). Of those, 11% experience liver cirrhosis or liver failure. Each year in the U.S., around 26,000 deaths are attributed to cirrhosis. That's why preventing the progression from non-alcoholic fatty liver disease to cirrhosis is critical.

Since there are no specific medications to treat MASLD, healthcare providers typically recommend diet and lifestyle changes to prevent further liver damage. In some cases, MASLD can be reversed if caught in the early stages.

Recently, researchers discovered that a trendy class of diabetes/weight loss medications called glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as Ozempic and Wegovy, may be effective at lowering the risk of cirrhosis in people with MASLD.

The findings show that GLP-1s may be a new prevention strategy for cirrhosis that could help reduce mortality risks from this challenging condition.

Liver benefits from taking GLP-1s versus other diabetes drugs

The study, published on September 16 in JAMA Internal Medicine, used data from the National Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry to compare liver outcomes of people with MASLD and type 2 diabetes.

Specifically, they looked at who took GLP-1RAs (exenatide, dulaglutide, liraglutide, or semaglutide) or dipeptidyl peptidase 4 inhibitors (DPP-4is), including sitagliptin, saxagliptin, linagliptin, or alogliptin, to see how these medications impacted liver health.

The scientists found that participants without cirrhosis who used GLP-1RAs had a slightly lower risk of developing cirrhosis compared to those using DPP-4is.

Moreover, people in the GLP-1 group had a lower risk of cirrhosis complications, liver cancer, and mortality compared to the DPP-4i group, but the difference in complications was not statistically significant.

In addition, the researchers found no differences in outcomes among participants taking GLP-1s or DPP-4is who already had cirrhosis.

Though the study results require confirmation in clinical trials, the team suggests that since both drugs offered no benefit to people who already had cirrhosis, treating MASLD early with GLP-1s may be critical for preventing this condition.

"While cirrhosis is a clear risk factor for [liver cancer] and reducing cirrhosis by GLP-1 RA use should prevent [liver cancer], an independent confirmation of this relationship requires even larger studies than this one," the study's authors wrote. "In the meantime, the presence of MASLD can help with the prioritization of GLP-1 therapy in persons with diabetes."