Anything strong enough to do good can do bad.
In the long tradition of medicine's most consequential accidents, researchers at the Medical University of South Carolina discovered while studying kidney disease that formoterol — an asthma drug prescribed for decades — may reverse fatty liver disease by restoring the energy-producing capacity of damaged cells. The finding arrives at a moment when MASH, a progressive liver condition tied to obesity and diabetes, affects hundreds of millions worldwide and remains largely without effective treatment. Human trials are now underway, carrying the quiet possibility that a familiar, inexpensive drug might answer an urgent and growing need.
- MASH is silently advancing toward liver failure and transplantation in hundreds of millions of people, with only two moderately effective treatments approved and a rising tide of obesity and diabetes accelerating its spread.
- The discovery was almost accidental — mice being treated for kidney disease developed unexpectedly healthy livers, forcing researchers to ask a question they hadn't planned to ask.
- Laboratory results showed formoterol didn't merely slow liver damage in mice fed a high-fat diet — it reversed it, appearing to reawaken mitochondria and restore liver function at multiple biological levels.
- Real-world data from patients already taking beta-2 agonists for respiratory conditions showed meaningfully lower rates of cirrhosis and death, lending cautious human weight to the animal findings.
- A clinical trial now enrolling diabetic kidney disease patients — more than 60 percent of whom also have MASH — will test whether the drug's promise survives contact with human biology, dosing complexity, and time.
Researchers at the Medical University of South Carolina were not looking for a liver treatment when they found one. They were studying formoterol — a beta-2 agonist long prescribed for asthma and COPD — to see whether it could protect mice from diabetes-related kidney damage. It did. But the mice also developed far less liver fat than expected, and that unplanned observation became its own investigation.
In a dedicated study, mice fed a high-fat diet to simulate MASH — a progressive fatty liver disease affecting hundreds of millions globally — were treated with formoterol. The liver damage reversed. Lead researcher Joshua Lipschutz described the effect as operating on multiple levels, with the drug appearing to boost mitochondrial biogenesis, essentially reviving the cellular machinery that produces energy and sustains liver health. The reversal was visible at the histologic, ultrastructural, and functional levels — not a slowing of harm, but an undoing of it.
To test whether this translated beyond the laboratory, the team examined real-world data from patients already taking beta-2 agonists for respiratory conditions. Those patients showed significantly lower rates of cirrhosis and overall mortality — not proof of causation, but a meaningful signal that the effect might hold in humans.
The urgency behind this work is considerable. MASH progresses toward fibrosis, cirrhosis, and liver failure, and its prevalence is climbing alongside global rates of obesity and Type 2 diabetes. Two treatments have recently been approved — resmetirom and semaglutide — but both are only moderately effective. Formoterol, by contrast, is already established, widely used, and relatively inexpensive. If it works in humans, the road to clinical adoption could be far shorter than for a novel drug.
The team is now enrolling patients with diabetic kidney disease in a clinical trial — a population where MASH co-occurs in more than 60 percent of cases, making it, as Lipschutz describes it, a two-for-one study. The trial will address questions that mice cannot answer: optimal dosing, whether inhaled delivery reaches the liver adequately, and how durable any benefits prove to be. Researchers are careful to note that animal results don't always survive translation to humans, and that no drug is without risk. But the convergence of evidence — reversed liver damage, supportive human data, an established safety record, and a disease in desperate need of options — makes the case for testing a compelling one.
A team of researchers at the Medical University of South Carolina stumbled onto something unexpected while studying kidney disease. They were testing formoterol, a beta-2 agonist that has been prescribed for asthma and chronic obstructive pulmonary disease for decades, to see if it could help mice with diabetes-related kidney damage. The drug worked for that purpose—results published in 2024 showed promise. But the mice also developed less liver fat than expected. That observation, almost accidental, opened a new line of inquiry.
The liver finding was striking enough to warrant a dedicated study. The researchers designed a second experiment using mice fed a high-fat diet to mimic metabolic dysfunction-associated steatohepatitis, or MASH—a progressive form of fatty liver disease that now affects hundreds of millions of people globally. When they treated these mice with formoterol, the fatty liver reversed. Joshua Lipschutz, the division director of nephrology at MUSC and lead author, described the effect as working on multiple levels. The drug appeared to rev up the mitochondria, the cellular powerhouses that produce energy. By increasing mitochondrial biogenesis, formoterol seemed to rescue the liver from injury at the histologic, ultrastructural, and functional levels—not just slowing the damage but actually reversing it.
To ground the mouse findings in human reality, the team conducted a retrospective analysis of patients already taking beta-2 agonists for respiratory conditions. The real-world data showed something encouraging: people using these drugs had significantly lower rates of serious liver complications, including cirrhosis and all-cause mortality. This wasn't proof of causation, but it suggested the drug's effects might translate beyond the laboratory.
The timing of this discovery matters. MASH is one of the most urgent liver diseases facing public health. It develops when fat accumulation in the liver begins to drive ongoing injury, eventually leading to fibrosis, cirrhosis, liver failure, and the need for transplantation. Its prevalence is rising alongside obesity and Type 2 diabetes. When the MUSC team began their work, no drugs existed to treat MASH at all. Two therapies have since been approved—resmetirom and semaglutide—but both remain only moderately effective and carry side effects. Formoterol, by contrast, is already established, already safe, already prescribed to millions of people. If it works in humans the way it works in mice, the path to clinical use could be dramatically shortened.
Lipschutz and his colleagues are currently enrolling patients in a clinical trial, though not specifically for MASH. They're recruiting people with diabetic kidney disease—the same metabolic dysfunction that drives both conditions. More than 60 percent of patients with diabetic kidney disease also have MASH, making this what Lipschutz calls a two-for-one study. The trial will answer practical questions that mouse models cannot: What dose would be most effective for metabolic disease in humans? Will inhaled delivery reach the liver and kidneys adequately? How long do any benefits last?
The researchers are careful about their claims. Lipschutz notes that not everything working in mice translates to humans. The human data so far shows association, not causation. And he reminds patients that no drug is completely safe—anything strong enough to do good can do harm. But the convergence of findings—the mouse reversal, the retrospective human data, the established safety profile, the urgent need—creates a compelling case for testing. If the trial succeeds, formoterol could become a relatively inexpensive, well-tolerated option for two of diabetes's most serious complications. For now, the work stands as a reminder that sometimes the most important discoveries come sideways, from research aimed at one problem that illuminates another.
Citações Notáveis
This actually reversed the pathology on multiple different levels. It kind of revs up the mitochondria so they work better.— Joshua Lipschutz, Division Director of Nephrology at MUSC
If you can repurpose something that's approved and already being used safely, that's kind of our dream as physician-scientists.— Joshua Lipschutz
A Conversa do Hearth Outra perspectiva sobre a história
How did researchers end up looking at liver disease when they were studying kidneys?
They were testing formoterol in mice with diabetes-related kidney injury. The drug worked for that, but they noticed the mice also had less liver fat than expected. That observation prompted them to ask whether the same mechanism might help the liver directly.
What exactly is formoterol doing inside the cells?
It appears to boost mitochondrial function—essentially revving up the cellular engines that produce energy. By increasing mitochondrial biogenesis, the drug seems to rescue cells from metabolic injury.
But this is all mouse data. Why should anyone believe it will work in people?
That's the right skepticism. The team also looked at real patients already taking beta-2 agonists for asthma and found lower rates of serious liver complications. It's not proof, but it's a signal worth following.
What makes this different from the two drugs already approved for MASH?
Those drugs slow progression. Formoterol actually reversed the damage in mice—at multiple levels. And formoterol is already approved, already safe, already used by millions. That could compress the timeline dramatically.
So they're testing it now?
They're enrolling patients with diabetic kidney disease. But since over 60 percent of those patients also have MASH, the trial will answer questions about both diseases at once.
What's the biggest remaining uncertainty?
Whether it works the same way in human bodies as it does in mice. And practical questions like the right dose, whether inhaled delivery reaches the liver adequately, and how long benefits last.