Researchers in Barcelona report that the lipid drug pemafibrate and the blood-pressure medicine telmisartan reduced diet-induced liver fat in rats and in a zebrafish model of fatty liver disease, with a half-dose combination performing as well as full doses of either drug alone. The work, published in Pharmacological Research, also describes a role for the PCK1 protein in telmisartan’s liver effects and argues that clinical trials would be needed to confirm any benefit in people.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is described by the study authors as the most prevalent liver disease worldwide, with recent estimates putting adult prevalence at roughly 38%.
In a paper published in Pharmacological Research (2025; volume 218: article 107860), a research team based at the University of Barcelona reported results from experimental models designed to mimic early MASLD driven by diet. In those models, animals were fed a high-fat, high-fructose diet that induced fat accumulation in the liver.
According to the University of Barcelona team’s report, treatment with either pemafibrate or telmisartan reduced hepatic fat accumulation. The study also reported that giving the drugs together—each at half of the individual dose—was as effective as a full dose of either drug alone in reducing liver lipid accumulation in the rat model.
The researchers argued that using two medicines that act on different disease pathways could offer advantages over single-drug therapy by enabling lower doses. As professor Marta Alegret was quoted as saying in the University of Barcelona’s release, “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.”
The study further proposed different mechanisms for each drug. Pemafibrate’s antisteatotic effect was described as being mediated through PPARα-driven increases in fatty-acid catabolism. Telmisartan’s liver effect was reported to be independent of PPAR modulation and linked instead to increased hepatic expression of phosphoenolpyruvate carboxykinase 1 (PCK1). The authors reported that telmisartan restored PCK1 levels in MASLD livers and that metabolomics suggested this shift redirected fructose-derived metabolism away from lipid synthesis toward glucose synthesis and downstream pathways in a way that preserved overall glucose homeostasis.
In the university’s summary, Alegret said the two-drug approach could be attractive for cardiometabolic risk factors often seen alongside MASLD, noting that the combination “lowers blood pressure and cholesterol levels,” which “would result in a lower cardiovascular risk.”
The researchers cautioned that the work remains preclinical. They said clinical studies would be required to determine whether benefits observed in rats and the zebrafish model translate to humans, and they highlighted open questions about whether similar effects would be seen in later-stage disease when fibrosis is present. The team said it is planning additional animal studies involving diet-induced liver fibrosis and models combining liver disease and cardiovascular complications.
