A new study published in JAMA Internal Medicine indicates that GLP-1 receptor agonists, including semaglutide (Ozempic/Wegovy), may significantly reduce the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) to cirrhosis in patients with diabetes. The research, led by Dr. Fasiha Kanwal from Baylor College of Medicine, suggests that early intervention with these medications can alter the course of liver disease in this population.
The study tracked over 32,000 veterans with diabetes and MASLD, comparing those treated with GLP-1 agonists to those receiving DPP-4 inhibitors. The results showed a 14% reduction in the risk of progressing to cirrhosis and an 11% decrease in mortality among GLP-1 users. These benefits typically emerged within 18 to 24 months of initiating GLP-1 therapy.
Impact on Liver Health
MASLD, characterized by excessive fat accumulation in the liver, is often associated with obesity and diabetes. If left untreated, it can lead to cirrhosis, liver cancer, and the need for liver transplantation. A healthy liver typically contains 5% or less fat by weight, whereas MASLD can elevate fat levels to dangerous proportions.
The study's findings underscore the importance of early intervention. "The protective association was not seen in patients with existing cirrhosis, underscoring the importance of treatment earlier in the [MASLD] disease course," Kanwal's group noted. This highlights a critical window of opportunity for GLP-1 agonists to prevent irreversible liver damage.
Mechanism of Action
The beneficial effects of GLP-1 agonists on liver health are likely multifactorial. These drugs reduce body weight, improve glycemic control, and decrease inflammation—all of which contribute to the progression of MASLD. Prior studies have even demonstrated the potential of GLP-1 medications to reverse fatty liver disease.
Future Directions
While the current study focused on existing GLP-1 agonists, newer agents in development may offer even greater benefits. For instance, Eli Lilly's experimental GLP-1 drug, retatrutide, has shown promise in reducing liver fat in obese individuals. Additionally, survodutide, another experimental GLP-1 drug, demonstrated improved liver health in 83% of patients with fatty liver disease in a trial funded by Boehringer Ingelheim and published in the New England Journal of Medicine.
Although the study did not find sufficient data to determine whether GLP-1 agonists could lower liver cancer risks, the overall findings suggest a significant role for these medications in managing and preventing the progression of diabetes-linked liver disease.
