Metabolic dysfunction-associated steatotic liver disease is the most common liver disease in the world, affecting about one third of the adult population. This disorder is characterized by the accumulation of fat in liver cells, which has severe liver consequences and is also associated with a high mortality rate from cardiovascular disease.
Now, a University of Barcelona study published in the journal Pharmacological Research shows that pemafibrate and telmisartan, two drugs already approved for other conditions, effectively reduce fat accumulation in laboratory animal models of metabolic liver disease. Furthermore, the study suggests that this combination of drugs may help to reduce both liver involvement and associated cardiovascular complications. These results open the door to the development of safer and more effective treatments for this disease, for which current therapeutic options are very limited.
The study has been carried out by a team led by Marta Alegret, professor at the UB's Faculty of Pharmacy and Food Sciences, the Institute of Biomedicine of the UB (IBUB) and the CIBER Area for Physiopathology of Obesity and Nutrition (CIBEROBN). The study has been carried out in collaboration with researchers from the Santa Creu i Sant Pau Hospital Research Institute, the Hospital Clínic de Barcelona, the CIBER Area for Cardiovascular Diseases (CIBERCV) and Uppsala University (Sweden).
Drug repurposing, a promising and cost-effective strategy
So far, most new compounds studied for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) - formerly known as fatty liver disease - have failed in clinical trials for several reasons, including safety concerns. In this context, the drug repurposing with a known and acceptable adverse effect profile in humans is an attractive, safe and more cost-effective strategy. This therapeutic repositioning is of particular interest in the early, usually asymptomatic, stages of the disease.
"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.
Specifically, researchers have analysed the repurposing potential against MASLD of the single or combined administration of a lipid-lowering drug (pemafibrate) and an antihypertensive (telmisartan), both marketed - the former only in Japan - for the treatment of pathologies related to cardiovascular risk: hyperlipidaemia and hypertension, respectively. "Mortality from cardiovascular causes is significant in patients with MASLD, and often these patients also have these two risk factors together," Alegret stresses.
