Common asthma drug formoterol shows promise as therapy to reverse fatty liver

Medical University of South Carolina researchers have reported that formoterol, a long-established beta-2 adrenergic receptor agonist used in asthma and chronic obstructive pulmonary disease, has been shown to reverse fatty liver disease in mouse models and was associated with lower rates of serious liver outcomes in retrospective human data

A research team at the Medical University of South Carolina (MUSC), Charleston, USA, has reported evidence that formoterol – a long-established asthma medicine – may offer a novel therapeutic route for metabolic dysfunction-associated steatohepatitis (MASH), a progressive form of fatty liver disease that affects large numbers of people worldwide and has become a major driver of liver transplantation.

The findings suggest that formoterol may act beyond the airways to influence metabolic disease through the beta-2 adrenergic receptor pathway. Formoterol is a beta-2 adrenergic receptor agonist that has been prescribed for decades to help to open airways in people with asthma and chronic obstructive pulmonary disease (COPD). The MUSC has reported that the study explored formoterol in MASH after earlier kidney research produced an unexpected liver-related observation.

The work began during experiments in mouse models of kidney injury linked to diabetes. The original aim was to test whether formoterol could reduce kidney damage. Those studies – published in American Journal of Physiology – Renal Physiology in 2024 – found evidence of benefit in the kidney. During that work, however, researchers noticed that mice which received formoterol also appeared to have less liver fat.

“Kind of unexpectedly, we found that the liver damage also reversed,” said Dr. Joshua Lipschutz, division director of nephrology and ‘Arthur Williams Endowed Chair in Nephrology’ at the MUSC.

The study was conducted with Dr. Jessica Hartman, and Dr. Don Rockey, at MUSC. Brennan Winkler, a doctoral candidate in the Lipschutz laboratory, and Hartman laboratory doctoral candidate Kristina Stayer, were named as co-first authors.

That unexpected result prompted a second line of research that focused directly on the liver and asked whether the same beta-2 pathway could influence metabolic disease across more than one organ. To test the hypothesis, the team used a high-fat diet mouse model designed to replicate key features of MASH. In the follow-up study, formoterol treatment was associated with reversal of fatty liver pathology.

“This actually reversed the pathology on multiple different levels,” said Lipschutz.

The study also examined biological mechanisms that may help to explain the effect. The researchers found signs that formoterol may affect how cells produce and use energy, particularly through mitochondrial biogenesis, the process by which cells increase their mitochondrial content and capacity. Mitochondria are often described as the power stations of the cell because they convert nutrients into usable cellular energy. In metabolic disease, mitochondrial dysfunction can contribute to tissue injury, fat accumulation and inflammation.

“It looked like formoterol was rescuing the injury by increasing mitochondrial biogenesis,” said Lipschutz.

“It kind of revs up the mitochondria so they work better,” he added.

To add a human data component, the investigators also conducted a retrospective analysis of patients who had already received beta-2 agonists for respiratory conditions. In that real-world dataset, use of the drugs was associated with significantly lower rates of several serious liver-related outcomes, including cirrhosis and all-cause mortality. The published paper reported that long-acting beta agonists, particularly formoterol, raised the possibility of a novel treatment strategy for MASH, although the authors framed the finding as a basis for further study rather than proof of clinical efficacy.

MASH is the progressive form of metabolic dysfunction-associated steatotic liver disease – previously called non-alcoholic fatty liver disease. It represents the stage at which fat accumulation in the liver begins to drive persistent injury, inflammation and tissue damage. Over time, this process can lead to fibrosis, cirrhosis, liver failure and – in severe cases – the need for liver transplantation. The condition has become more common in parallel with obesity, insulin resistance and type 2 diabetes, which has made it one of the most pressing long-term challenges in hepatology.

“At the time we started the study, there were no drugs approved to treat MASH,” said Lipschutz.

The treatment landscape has, however, since begun to shift where in the USA, resmetirom became the first approved treatment for adults with non-cirrhotic MASH with moderate to advanced liver fibrosis in 2024. The US Food and Drug Administration then approved semaglutide 2.4 mg – branded as Wegovy – in August 2025 for adults with non-cirrhotic MASH with moderate to advanced liver scarring. These approvals have changed the therapeutic context but have not removed the need for additional options, particularly for patients with overlapping metabolic, liver and kidney disease.

“All the current drugs for diabetic nephropathy only slow progression but they don’t reverse the damage. This drug actually reversed the damage at the histologic, ultrastructural and functional levels,” said Lipschutz.

Formoterol’s appeal lies partly in its established clinical history. Because it has already been used for many years in asthma and COPD, researchers have a substantial body of safety and prescribing experience on which to draw. If its metabolic effects can be confirmed in humans, that existing record could shorten the route to further clinical development compared with an entirely novel drug candidate.

“If you can repurpose something that’s approved and already being used safely, that’s kind of our dream as physician-scientists,” said Lipschutz.

Although the paper has focused on MASH, Lipschutz’s current clinical trial has begun to enrol patients with diabetic kidney disease. The overlap between diabetic nephropathy and MASH gives the study wider significance. The researchers noted that more than 60 per cent of patients with diabetic nephropathy also have MASH, which means the trial may allow the team to assess formoterol’s effect on both conditions. Both diseases arise from underlying metabolic dysfunction and are among the most serious complications associated with diabetes.

“So it is a two-for-one study,” said Lipschutz.

Existing evidence in both disease areas has supported the rationale for the trial, but important uncertainties remain.

“In both cases, there were human retrospective data suggesting that this could be working,” said Lipschutz.

The liver findings are based largely on mouse models and the human evidence so far is observational. Such data can show an association between beta-2 agonist use and lower rates of liver-related outcomes but it cannot prove that the drug caused those outcomes to improve. Confounding factors, differences between patient groups and prescribing patterns may all influence retrospective analyses.

Researchers must also resolve practical questions before formoterol could be considered as a possible treatment for MASH or diabetic kidney disease. These include the most effective dose for metabolic disease, whether inhaled delivery can produce sufficient effects in the liver or kidney and how durable any benefit may prove to be. Safety will also require careful evaluation, particularly if treatment has to continue for long periods or if higher systemic exposure proves necessary.

“No drug is completely safe. I always say to my patients: ‘Anything strong enough to do good can do bad,’” said Lipschutz.

The clinical trial now under way has been designed to begin to answer those questions. If it produces encouraging results, the findings could support further studies of formoterol as a repurposed therapy for diabetic kidney disease and MASH.

“If you could be treating them with a repurposed, relatively safe, inexpensive drug that could be a really good thing,” said Lipschutz.

For now, the work has highlighted how a decades-old respiratory medicine may hold untapped potential in metabolic disease. It has also shown how research in one organ system can reveal unexpected therapeutic possibilities in another. The central question now is whether the apparent reversal of liver and kidney damage seen in preclinical models can translate into meaningful clinical benefit for patients.

For further reading please visit: 10.1038/s44324-026-00108-2