A groundbreaking study from the University of Barcelona has unveiled promising results in the treatment of fatty liver disease using two well-established medications. Researchers identified that the drugs pemafibrate and telmisartan significantly reduced liver fat in animal models, showcasing not only improvements in liver health but also a reduction in cardiovascular risks when administered together.
Given the limited treatment options available for fatty liver disease, these findings suggest a potential new pathway that may offer a safer and more effective alternative to many experimental therapies currently under investigation.
Led by Marta Alegret, a professor at the University of Barcelona's Faculty of Pharmacy and Food Sciences, the research involved collaboration with prominent institutions including the Institute of Biomedicine of the UB (IBUB), the CIBER Area for Physiopathology of Obesity and Nutrition (CIBEROBN), and Uppsala University in Sweden.
The Significance of Repurposing Existing Drugs
Many experimental treatments for metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as fatty liver disease, have faced challenges in clinical trials due to safety concerns. This has led researchers to consider drug repurposing, which utilizes medications already approved for other conditions. This approach is not only faster and more cost-effective but also safer, particularly for the early stages of MASLD, which often do not exhibit symptoms.
"Our focus has been on preventing the disease from advancing to more severe stages. For a drug to be effective in these early phases, it must demonstrate a strong safety profile in humans," Alegret states. "This is why we explored already approved medications that could offer potential benefits for MASLD treatment," she adds.
The study tested pemafibrate, a lipid-lowering agent, alongside telmisartan, a blood pressure medication. While pemafibrate is currently available only in Japan, telmisartan is widely prescribed globally. Alegret emphasizes the significant cardiovascular mortality associated with MASLD, which often coexists with these two risk factors.
Promising Results from Animal Testing
To investigate the drugs' efficacy, researchers conducted tests on rats and zebrafish larvae, which serve as excellent models for studying liver disease due to their metabolic similarities to humans. The results were remarkable; the combination of pemafibrate and telmisartan effectively reversed liver fat accumulation induced by a high-fat, high-fructose diet. Notably, administering half doses of both drugs was as effective as full doses of either drug alone.
"Combining therapies that target different pathways may provide a superior strategy compared to single-drug treatments, potentially enhancing efficacy while minimizing toxicity," Alegret notes.
In addition to improving liver health, the treatment may also lower blood pressure and cholesterol levels, contributing to reduced cardiovascular risks.
Understanding the Mechanism
The study further revealed that pemafibrate and telmisartan operate through distinct biological pathways. For the first time, researchers highlighted the role of the PCK1 protein in telmisartan's ability to reduce liver fat. In MASLD-affected animals, PCK1 levels were found to be lower than normal, and treatment with telmisartan restored these levels, altering the liver's nutrient processing.
Although the findings are promising, they are still in the early stages, derived from animal studies. Clinical trials are necessary to determine if these benefits translate to human patients.
The research team is now investigating whether the same drug combination could be effective in more advanced stages of MASLD, particularly in the presence of liver fibrosis, and exploring dual models that incorporate both liver disease and cardiovascular conditions.