New hope in fatty liver disease: a drug combination that could reverse MASLD
Fatty liver disease, now increasingly called MASLD (Metabolic Associated Steatosis with Liver Disease), affects millions worldwide and is rising in prevalence alongside obesity and sedentary lifestyles. While lifestyle changes remain essential, researchers have long searched for therapies that can halt or reverse fat buildup in the liver. A new study from the University of Barcelona presents a promising option: combining two well-known cardiovascular drugs, pemafibrate and telmisartan, may actively reduce liver fat and improve liver health in MASLD models.
What the study found
Published in Pharmacological Research, the study reports that using pemafibrate together with telmisartan led to a significant reduction in liver fat in MASLD models. Pemafibrate is a selective PPAR-α agonist that promotes lipid metabolism and fatty acid oxidation, while telmisartan is an angiotensin II receptor blocker (ARB) commonly used to treat hypertension. When used in combination, these drugs appear to exert complementary effects beyond what either can achieve alone, lowering hepatic lipid accumulation and improving cardiovascular risk markers.
Crucially, MASLD is closely linked to cardiovascular disease, so a treatment that addresses both liver fat and heart health holds particular appeal. Many MASLD patients contend with high blood pressure and dyslipidemia; a therapy with dual benefits could streamline care and potentially reduce the progression to more serious liver conditions.
How pemafibrate and telmisartan work together
Pemafibrate acts as a selective PPAR-α modulator. It enhances lipid metabolism in the liver, boosts fatty acid oxidation, and reduces triglyceride synthesis. In animal studies, pemafibrate alone has already shown a capacity to curb liver fat accumulation.
Telmisartan is an ARB that lowers blood pressure but also influences metabolic pathways. It can improve insulin sensitivity, reduce inflammatory signaling, and alter lipid processing. Prior research has explored ARBs and ACE inhibitors for NAFLD/MASLD due to potential anti-fibrotic and metabolic benefits.
By targeting distinct yet interconnected pathways—direct hepatic lipid handling and systemic metabolic/inflammatory signaling—the combination may interrupt the cycle that drives fat buildup and liver injury. The researchers also highlighted a potential role for the protein PCK1 (phosphoenolpyruvate carboxykinase 1) in regulating hepatic fat metabolism, suggesting deeper biochemical mechanisms behind the observed effects.
Why this matters for patients and clinicians
MASLD affects up to one in three adults globally and remains a leading cause of chronic liver disease. While lifestyle management is vital, pharmacologic options have been limited. A therapy that simultaneously lowers liver fat and reduces cardiovascular risk could redefine treatment paradigms, especially given that both pemafibrate and telmisartan are already approved for other indications. This could accelerate translation into human trials and, ultimately, clinical practice.
Another practical advantage is safety and familiarity. Drug repurposing leverages established safety data, potentially shortening the path to human testing for liver-specific outcomes. Early-stage intervention in MASLD could also prevent progression to steatohepatitis or fibrosis, preserving liver function and reducing long-term complications.
What remains before this becomes standard care
Current findings come from rat and zebrafish models, not yet from human patients. Translating animal results to people often presents challenges, and optimal dosing for liver-specific effects must be determined. Additionally, drug–drug interactions, long-term safety, and effectiveness across diverse patient populations require careful study in phased clinical trials (Phase 1–3).
Researchers emphasize that the combination may be most effective in early MASLD, with later-stage disease potentially needing additional or alternative therapies. Ongoing and future trials will aim to identify which patients stand to benefit most and how to monitor response through liver enzymes, imaging, and, when appropriate, biopsies.
The road ahead
The possibility of repurposing pemafibrate and telmisartan offers a hopeful avenue for a disease with limited pharmacologic options. If future human trials confirm safety and efficacy, clinicians could one day prescribe a dual-action regimen that tackles both liver fat and cardiovascular risk, changing the trajectory of MASLD for millions.
