A recent study from the University of Barcelona suggests a potential breakthrough using medications that are already available. Researchers found that two drugs, pemafibrate and telmisartan, were able to significantly reduce liver fat in animal models of this disease. Even more encouraging, using the two together appeared to not only improve liver health but also reduce related cardiovascular risks.

Because treatment options for this condition remain limited, the findings point to a possible new approach that could be both safer and more effective than many experimental therapies.

The research was led by Marta Alegret, a professor at the University of Barcelona’s Faculty of Pharmacy and Food Sciences, and involved collaborations with several major research institutions, including the Institute of Biomedicine of the UB (IBUB), the CIBER Area for Physiopathology of Obesity and Nutrition (CIBEROBN), and Uppsala University (Sweden).

Why Repurposing Existing Drugs Matters

Many experimental drugs for metabolic dysfunction-associated steatotic liver disease (MASLD) — formerly known as fatty liver disease — have not made it through clinical trials, often due to safety concerns. This has pushed scientists to explore drug repurposing, which involves using medications that are already approved for other conditions.

This strategy can be faster, more cost-effective, and safer, especially for early stages of MASLD that typically do not show symptoms.

“We have focused on these phases with the aim of preventing the disease from progressing to more severe stages. But for a drug to be used in these early stages, it must have a good safety profile in humans,” explains Marta Alegret. “That is why we have studied drugs already on the market for other pathologies, which have been shown to be very safe and could have a potential benefit in the treatment of MASLD,” she adds.

The team tested a lipid-lowering drug (pemafibrate) and a blood pressure medication (telmisartan), both used to manage cardiovascular risk. Pemafibrate is currently marketed only in Japan, while telmisartan is widely prescribed worldwide. “Mortality from cardiovascular causes is significant in patients with MASLD, and often these patients also have these two risk factors together,” Alegret stresses.

Animal Models Reveal Strong Effects

To better understand how the drugs work, researchers tested them in both rats and zebrafish larvae. Zebrafish have become a valuable model for studying liver disease because their metabolism and liver function share important similarities with humans, while also allowing faster and more affordable experiments.

The results were striking. The combination of pemafibrate and telmisartan reversed liver fat buildup caused by a diet high in fat and fructose. In rats, using half doses of both drugs together was just as effective as using a full dose of either drug alone.

“Combination therapy with drugs acting on different pathogenic pathways may be a better strategy than monotherapy, thanks to possible synergistic effects and reduced toxicity related to the use of lower doses of each drug,” Alegret points out.

Beyond improving liver health, the treatment may also lower blood pressure and cholesterol levels. “It lowers blood pressure and cholesterol levels, and all this would result in a lower cardiovascular risk,” she stresses.

How the Drugs Work Differently

The study also revealed that the two drugs act through different biological pathways. For the first time, researchers identified an important role for the PCK1 protein in how telmisartan reduces liver fat.

“Telmisartan is a drug that has been used in other models of MASLD, but mostly in more advanced stages of the disease, and its beneficial effects have been attributed mainly to anti-inflammatory and anti-fibrotic effects. But in the early stages of the disease there is no inflammation or fibrosis yet, only lipid accumulation,” explains the researcher.

In animals with MASLD, levels of PCK1 in the liver were lower than normal. Treatment with telmisartan restored these levels, shifting how the liver processes nutrients.

“This increase in PCK1 diverts the flux of metabolites from lipid synthesis to glucose synthesis. This increase in glucose production could be negative if the glucose were exported and accumulated in the blood, as it could lead to diabetes, but we have noticed that this is not the case,” says the UB professor.

Still Early, but Encouraging

Although the results are promising, the research is still at an early stage. The findings come from animal studies, and more work is needed before the treatment can be tested in people.

“In order to be translated into a treatment for MASLD patients, clinical studies would be needed to show that the benefits observed in animal models also occur in humans,” says Alegret.

The team is now exploring whether the same drug combination could work in more advanced stages of the disease, particularly when liver fibrosis is present. They are also developing new models that include both liver disease and cardiovascular conditions to see if the benefits extend beyond the liver.

“In addition, we will develop a dual model involving liver fibrosis and cardiovascular disease to see if the beneficial action is observed not only in the liver, but also in the reduction of atherosclerosis,” he concludes.