Anything strong enough to do good can do bad
In the quiet work of studying kidney disease, researchers at MUSC encountered an unexpected guest — a decades-old asthma drug quietly reversing fatty liver damage in mice. Formoterol, long trusted to open airways, may carry a deeper gift: the ability to restore cellular energy production in a liver under metabolic siege. The disease it may address, MASH, burdens hundreds of millions worldwide and remains one of medicine's most stubborn unsolved problems. Science, as it sometimes does, found a new door by walking through a familiar one.
- MASH — fatty liver's most destructive form — affects hundreds of millions globally and is a leading driver of liver transplantation, yet effective treatments have remained elusive until now.
- A chance observation during kidney research revealed that formoterol, a common asthma medication, dramatically reduced liver fat in mice fed a high-fat diet, forcing researchers to rethink the drug's potential.
- Retrospective human data added urgency to the finding: patients already taking beta-2 agonists for respiratory conditions showed significantly lower rates of cirrhosis and death.
- The drug's appeal lies in its history — inexpensive, long-approved, and well-understood — meaning repurposing it could bypass years of safety trials that new compounds require.
- A clinical trial now underway in diabetic kidney disease patients will serve double duty, testing formoterol against MASH simultaneously since the two conditions so frequently overlap.
- Critical unknowns persist — optimal dosing, whether inhaled delivery reaches the liver effectively, and whether benefits hold over time — keeping cautious optimism in check.
A research team at MUSC set out to study kidney damage and found something they weren't looking for. The drug they were testing — formoterol, a beta-2 agonist used for decades in asthma treatment — worked as expected on the kidneys, but the mice also developed far less liver fat. That accidental observation became a deliberate investigation.
The disease they turned toward is MASH, the progressive form of fatty liver disease, in which accumulated fat actively destroys the organ, leading to fibrosis, cirrhosis, and eventual failure. Hundreds of millions carry it worldwide, and it is among the leading reasons people need liver transplants. Doctors have had little to offer them.
In follow-up experiments using mice on a high-fat diet, formoterol reversed the fatty liver. The mechanism appeared to involve mitochondrial biogenesis — the drug seemed to revive the cellular power plants responsible for energy production, rescuing cells from metabolic injury. The findings were published in npj Metabolic Health and Disease.
To probe whether this translated to people, the team analyzed real-world data from patients already prescribed beta-2 agonists for respiratory conditions. Those patients showed meaningfully lower rates of cirrhosis and all-cause mortality. Lead researcher Joshua Lipschutz was careful to note that association is not causation — but the signal was real.
Formoterol's greatest asset may be its familiarity. It is cheap, long-approved, and carries a well-documented safety record. Repurposing it would sidestep much of the regulatory burden facing entirely new compounds. A clinical trial now underway in diabetic kidney disease patients will also assess MASH outcomes, since more than 60 percent of those patients develop the liver condition as well — effectively testing one drug against two diseases at once.
Questions remain: the right dose for metabolic disease, whether inhaled delivery reaches the liver adequately, and whether gains persist. Lipschutz offered a measured reminder that no drug is without risk. But for now, the work stands as a testament to how discovery often arrives sideways — a team studying one organ, finding answers in another.
A team of researchers at MUSC set out to study kidney damage in mice, but stumbled onto something unexpected in the liver. They were testing formoterol, a beta-2 agonist that has been used for decades to open airways in asthma and chronic obstructive pulmonary disease patients. The drug worked as intended for kidney injury—results published in 2024 showed promise—but the mice also developed significantly less liver fat. That accidental observation prompted a deliberate pivot: could the same mechanism that protected the kidneys also reverse fatty liver disease?
The condition they were now chasing is called MASH, metabolic dysfunction-associated steatohepatitis. It is the progressive form of fatty liver, where accumulated fat begins to actively damage the organ. Left untreated, it leads to fibrosis, cirrhosis, liver failure, and transplantation. Hundreds of millions of people worldwide carry the disease, and it ranks among the leading reasons people need new livers. Yet until recently, doctors had almost nothing to offer them.
In their follow-up study, the MUSC team used mice fed a high-fat diet to model MASH. When they treated these animals with formoterol, the fatty liver reversed. Joshua Lipschutz, the division director of Nephrology who led the work alongside Jessica Hartman and Don Rockey, explained that the drug appeared to work by revving up the mitochondria—the cellular power plants that produce energy. By enhancing mitochondrial biogenesis, formoterol seemed to rescue cells from metabolic injury at multiple levels. The findings were published in npj Metabolic Health and Disease.
But mouse studies are one thing. To test whether this translated to humans, the team conducted a retrospective analysis of real patients who had already been prescribed beta-2 agonists for respiratory conditions. The data showed something striking: people using these drugs had significantly lower rates of cirrhosis and all-cause mortality compared to those who did not. Association is not causation, and Lipschutz was careful about that distinction. Yet the signal was there.
What makes formoterol particularly attractive as a potential therapy is its pedigree. It has been safely prescribed for decades. The drug is inexpensive. If its metabolic effects hold up in human trials, the regulatory path forward would be far shorter than developing something entirely new. "If you can repurpose something that's approved and already being used safely, that's kind of our dream as physician-scientists," Lipschutz said.
The team is now running a clinical trial in patients with diabetic kidney disease—another condition formoterol may help. But there is a bonus built into the study design: more than 60 percent of people with diabetic kidney disease also develop MASH, since both conditions stem from the same underlying metabolic dysfunction. So the trial will effectively test formoterol against two diseases at once.
Still, significant questions remain unanswered. Not everything that works in mice translates to humans. Researchers need to determine the right dose for metabolic disease, whether inhaling the drug will deliver enough to the liver and kidneys, and whether benefits persist over time. Lipschutz reminds patients and colleagues alike that no drug is completely safe. "Anything strong enough to do good can do bad," he said.
For now, the work stands as a reminder that discovery often arrives sideways. A team studying one organ found answers in another. If the clinical trial succeeds, a medication that has quietly opened airways for generations might soon be asked to do something far more ambitious: reverse the damage of a disease that affects hundreds of millions and leaves few good options in its wake.
Notable Quotes
This actually reversed the pathology on multiple different levels. It looked like formoterol was rescuing the injury by increasing mitochondrial biogenesis—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
The Hearth Conversation Another angle on the story
How did you end up looking at the liver at all? You were studying kidneys.
We were testing formoterol in mouse models of kidney injury from diabetes. The drug worked—we published that. But we noticed the mice also had less liver fat. That wasn't the plan, but it was too interesting to ignore.
So you pivoted the whole study?
We did. We designed a new experiment specifically for the liver, using mice fed a high-fat diet to mimic MASH. Same drug, same mechanism. And yes, the fatty liver reversed.
What's the mechanism? How does an asthma drug fix a liver problem?
It appears to boost mitochondrial function—the cellular power plants. The drug revs them up so they work better, which helps cells produce and use energy more efficiently. That seems to rescue the liver from metabolic injury.
But you also looked at real patients, not just mice.
We did a retrospective analysis of people already taking beta-2 agonists for asthma or COPD. They had significantly lower rates of cirrhosis and mortality. It's not proof of causation, but it's a signal worth pursuing in a proper trial.
What's the dream scenario here?
We repurpose a drug that's already approved, safe, inexpensive, and widely used. If it works in humans the way it works in mice, we've just handed doctors a tool for a disease that has almost no good options right now.