October 14, 2025

Antihypertensive and lipid-lowering therapies demonstrate effectiveness in managing steatotic liver disease

Common Heart Medications Show Promise for Treating Fatty Liver Disease

Metabolic dysfunction-associated steatotic liver disease (MASLD) — formerly known as fatty liver disease — is the most widespread liver disorder globally, affecting nearly one-third of adults. It is marked by the excessive buildup of fat in liver cells, which not only damages the liver but also greatly increases the risk of cardiovascular death.

Now, researchers from the University of Barcelona have discovered that two existing medications — pemafibrate and telmisartan — significantly reduce fat accumulation in laboratory models of metabolic liver disease. Their findings, published in the journal Pharmacological Research, suggest that combining these drugs may improve both liver health and cardiovascular outcomes, paving the way for new and safer treatment options for a condition that currently lacks effective therapies.


A New Use for Existing Drugs

The study was led by Professor Marta Alegret from the Faculty of Pharmacy and Food Sciences at the University of Barcelona, in collaboration with scientists from the Santa Creu i Sant Pau Hospital Research Institute, Hospital Clínic de Barcelona, the CIBER networks for Obesity (CIBEROBN) and Cardiovascular Diseases (CIBERCV), and Uppsala University (Sweden).

Because most newly developed drugs for MASLD have failed in clinical trials due to safety or efficacy issues, the research team explored the strategy of drug repurposing — identifying new uses for existing, well-tested medications. This approach can speed up the development of treatments and reduce costs while ensuring patient safety.

“We focused on the early stages of MASLD, when patients are often asymptomatic but treatment could still prevent disease progression,” explained Alegret. “For this reason, it was essential to study drugs that already have an excellent safety profile in humans.”


Testing Pemafibrate and Telmisartan

Researchers investigated the individual and combined effects of pemafibrate, a lipid-lowering agent approved in Japan, and telmisartan, a widely used antihypertensive drug. Both medications are commonly prescribed for conditions that often coexist with MASLD, such as high cholesterol and hypertension — two major cardiovascular risk factors.

To evaluate their effects, the team tested the drugs in rat and zebrafish models of fatty liver disease. The combination of both medications was found to reverse diet-induced fat buildup in the liver. Remarkably, half-doses of each drug together were as effective as full doses of either drug used alone.

“Combination therapy targeting different disease pathways may be more effective and less toxic than monotherapy,” said Alegret. “In addition to improving liver fat metabolism, this dual approach also lowers blood pressure and cholesterol, reducing overall cardiovascular risk.”


Different Mechanisms, One Outcome

The study also revealed that the two drugs reduce liver fat through distinct biological mechanisms. For the first time, the researchers identified a key role for the PCK1 protein in the liver-fat-lowering effect of telmisartan.

“Telmisartan has been studied before, but mainly in later stages of MASLD, when inflammation and fibrosis are already present,” noted Alegret. “We discovered that in early disease, telmisartan restores normal PCK1 levels, redirecting metabolic pathways away from fat production and toward glucose generation — without increasing blood glucose levels.”


Promising, but Still Preliminary

While the results are encouraging, the research was conducted in animal models, and further clinical studies in humans will be needed before the findings can be translated into patient care.

“These results are an important first step,” said Alegret. “The next goal is to confirm whether these drugs can produce similar benefits in human patients with early-stage or advanced MASLD.”

The team is now conducting follow-up studies using models of diet-induced liver fibrosis and combined liver–cardiovascular disease, aiming to determine whether the dual therapy can prevent both liver scarring and atherosclerosis.

“Ultimately, our goal is to find safe, effective, and accessible treatments that not only protect the liver but also lower cardiovascular risk,” Alegret concluded.

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