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By Hannah Millington
Health Reporter
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Using two types of cardiovascular drugs together could help to treat fatty liver disease and reduce the number of severe cases.
This is the finding of researchers from the University of Barcelona (UB), who discovered that pemafibrate and telmisartan effectively reduced fat accumulation in laboratory animal studies of metabolic dysfunction-associated steatotic liver disease (MASLD).
MASLD is the most common chronic liver condition in the U.S., affecting about 25 percent of all adults. It accounts for a range of conditions all of which are characterized by extra fat in liver cells that do not result from alcohol consumption.
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“To date, monotherapy has been the predominant pharmacological strategy aiming to treat MASLD. However, given the complexity of MASLD and the successful use of combination therapies for other metabolic diseases, we believe that multiple drug therapy is a better strategy,” paper author professor Marta Alegret told Newsweek.
“The rationale of combining pemafibrate with telmisartan is based on three facts: a) both are drugs already used in humans, so their safety is proven; b) they possess complementary mechanisms of action to reduce liver lipids [fats]; and c) both compounds reduce cardiovascular risk, which is high in individuals with MASLD.”
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Alegret explained that telmisartan is widely used as an antihypertensive in approximately 90 countries, including the U.S., Japan and across Europe. In the U.S., telmisartan is available as a generic and under the brand name Micardis. Pemafibrate, meanwhile, is licensed only in Japan, where it has been approved since July 2017 for the treatment of dyslipidemia and hypertriglyceridemia.
According to the team, most of the new compounds previously studied for MASLD treatment have failed in clinical trials, for reasons including efficacy and safety. This study suggests the combination of these two existing drugs, however, may help to reduce both liver problems and associated cardiovascular complications.
“Our results demonstrate that both compounds, alone or combined, effectively reduce liver lipid levels in our rat model, which is a model of the initial stage of MASLD. Thus, we suggest that these compounds could be used to treat these early steps of the pathology, preventing the progression of the disease towards advanced phases," said Alegret.
Lifestyle changes such as eating a balanced diet, exercising and maintaining a healthy weight can initally help to reduce the build up of fat. Meanwhile, in cases with liver damage (fibrosis or cirrhosis), patients may need medication or, in severe cases, a liver transplant.
Alegret acknowledged lifestyle modifications are the “cornerstone” of MASLD treatment, but added: “Nevertheless, poor adherence has resulted in an insufficient strategy to stop the progression across the disease spectrum for most patients."
This could increase the risk of complications relating to and outside of the liver.
“Therefore, if changes in daily habits such as diet and physical activity could be combined with some drug or drugs with a good safety profile, this intervention would have a greater chance of success than lifestyle changes alone.”
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The earlier stages of the disease are usually asymptomatic, making prompt detection important.
“Although MASLD should be suspected in patients with metabolic risk factors, it is frequently underdiagnosed,” said Alegret. “In our opinion early MASLD diagnosis and treatment are unmet clinical needs that, if properly addressed, could result in a reduction in the number of patients with severe MASLD and thus a reduction in mortality.”
In their investigations, the researchers applied the drugs to a rat model of the disease and then to a zebrafish larval model.
The combination of the two drugs was found to reverse the fat accumulation in the liver induced by a diet high in fat and fructose. In the rat model, the combined administration of half a dose of pemafibrate and half a dose of telmisartan was found to be as effective as a full dose of either drug in reducing fat accumulation.
The study also revealed each drug works by different mechanisms and describes, for the first time according to the researchers, the key role of the PCK1 protein in telmisartan-derived lipid lowering in the liver. The team found the amount of PCK1 protein in the livers of MASLD animals was reduced and that treatment with telmisartan restored its levels to normal.
Limitations of the study included only using female rats as a model. Clinical studies are now also needed to determine whether the treatment shows potential in humans.
“Although translation of the results to humans is not straightforward, preclinical evidence mostly shows beneficial effects, so we believe that patients could benefit from these treatments,” said Alegret.
The team are also looking into whether the drugs would be just as effective in more advanced stages of the disease, such as fibrosis, which they are positive about.
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Reference
Bentanachs, R., Ramírez-Carrasco, P., Braster, B., Emmanouilidou, A., Mujica, E., Rodrigo-Calvo, M., Rodríguez, C., Roglans, N., den Hoed, M., Laguna, J. C., & Alegret, M. (2025). Telmisartan reverses hepatic steatosis via PCK1 upregulation: A novel PPAR-independent mechanism in experimental models of MASLD. Pharmacological Research, 218, 107860. https://doi.org/10.1016/j.phrs.2025.107860
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