A study from the University of Barcelona found that two existing drugs significantly reduced liver fat in animal models of metabolic dysfunction-associated steatotic liver disease, offering a potential new approach to a condition affecting one in three adults worldwide.
Drug repurposing offers a faster path to treatment for early-stage fatty liver disease
Researchers tested pemafibrate, a lipid-lowering medication available only in Japan, and telmisartan, a widely prescribed blood pressure drug, in rats and zebrafish larvae. The combination not only lowered liver fat but likewise reduced associated cardiovascular risks, addressing the leading cause of death in patients with this liver condition. Because both drugs are already approved for other uses, repurposing them could bypass years of safety testing required for experimental therapies, particularly important for early disease stages where symptoms are absent but progression risks are high.
Up to 80% of people with type 2 diabetes have fatty liver disease, making it a central complication
Dr. Scott Isaacs noted that MASLD is extremely common in diabetes, affecting as many as 70 or 80% of patients, with up to 30% having the more severe inflammatory form known as MASH. One in five patients with type 2 diabetes already shows liver fibrosis, a precursor to cirrhosis and liver cancer. The American Association of Clinical Endocrinologists now classifies MASLD and MASH as core complications in its diabetes treatment algorithm, urging clinicians to screen systematically using liver enzymes, FIB4 scores, and elastography rather than treating liver fat as an incidental finding.
Weight loss remains a cornerstone of management, but drug therapies are gaining traction
Whereas a 5% reduction in body weight can decrease liver fat, achieving meaningful improvement in fibrosis typically requires at least 10% weight loss, a target difficult for many patients to sustain. Emerging therapies such as GLP-1 receptor agonists, dual agonists, and Resmetirom are now integrated into treatment algorithms for noncirrhotic MASH with moderate to advanced fibrosis, reflecting a shift toward pharmacologic intervention alongside lifestyle changes. However, access to these newer drugs remains limited by cost and availability, underscoring the potential value of repurposed medications like pemafibrate and telmisartan.
Zebrafish models accelerated discovery by mirroring human liver metabolism
Researchers chose zebrafish larvae for part of their study because the species shares key metabolic and liver function similarities with humans while enabling faster, more cost-effective experiments. The transparent embryos allowed real-time observation of drug effects on lipid accumulation, providing strong preliminary evidence that supported testing in rodent models. This approach highlights how unconventional models can expedite early-stage research without compromising biological relevance, especially when investigating repurposed drugs with established safety profiles.
Why are existing drugs being studied for fatty liver disease instead of developing new ones?
Many experimental drugs for MASLD have failed in clinical trials due to safety concerns, prompting researchers to explore repurposing medications already approved for other conditions. This strategy can be faster, more cost-effective, and safer, particularly for early-stage disease where long-term treatment is needed but symptoms are absent.
How significant is the link between fatty liver disease and cardiovascular risk?
Cardiovascular disease is the number-one cause of death in patients with MASLD, and the conditions often coexist. The study’s focus on drugs that manage both liver fat and cardiovascular risk reflects this dual threat, aiming to address the leading cause of mortality in this population.
Can weight loss alone reverse fatty liver disease?
A modest 5% weight loss can reduce liver fat, but reducing inflammation and fibrosis typically requires at least 10% weight loss. For many patients, achieving and maintaining this level of loss is challenging, which is why pharmacologic options are increasingly considered alongside lifestyle modifications.
What role do zebrafish play in liver disease research?
Zebrafish larvae are used as a model because their liver metabolism and function closely resemble humans’, allowing researchers to observe drug effects quickly and affordably. Their transparency enables real-time visualization of fat accumulation in the liver, making them valuable for early-stage screening of potential therapies.
