Weight-loss and diabetes drug semaglutide shows promise in fighting metabolic dysfunction-associated steatohepatitis and liver fibrosis. The once-weekly shot, marketed as Ozempic, Wegovy and Rybelsus, could be a breakthrough treatment for metabolic dysfunction-associated steatohepatitis (MASH), a serious and progressive form of fatty liver disease. So what’s the deal with semaglutide and MASH?
Published in April 2025 in the New England Journal of Medicine, an international team of metabolic medics says semaglutide could be the first drug-based therapy for MASH. Currently, this life-threatening liver disease has no approved pharmacological treatments, despite its well-known link to liver failure and liver cancer.
The results of this phase 3 clinical trial point to semaglutide as a useful tool to treat MASH with nearly 63% of participants experiencing reduced inflammation and approximately 37% showing less liver scarring.
MASH: The Silent Liver Disease on the Rise
MASH formerly known as non-alcoholic steatohepatitis (NASH) is a significant and increasingly common liver disease. The chronic liver condition develops when fat builds up in the liver, causing it to swell and scar. Over time, this damage can become so severe that the liver stops working altogether. MASH shares many of the same underlying drivers as obesity and type 2 diabetes. Current standards of care emphasize lifestyle changes aimed at weight loss. The idea is that if putting on weight correlates to more fat in the liver, not adding more should prevent MASH from getting worse. For many people, however, lifestyle changes aren’t enough.
This growing health issue has led to cross-border research efforts like the ESSENCE project (Essential Strategies to Stem the Epidemic of NASH in Canada and Europe). This international investigation focuses on finding better ways to treat MASH. Researchers looked at whether semaglutide, a drug already used to help people with type 2 diabetes and obesity, could also help people with MASH by reducing fat in the liver and giving it a chance to heal. They hypothesized that if semaglutide can support weight loss, it might also reduce the amount of fat stored in the liver. To test this idea, they conducted a randomized, placebo-controlled trial—the gold standard of clinical trials.
Methodology MASH Up
Researchers carried out a randomized, double-blind, placebo-controlled trial across 22 countries to test whether semaglutide could treat MASH. This study design allows scientists to directly compare outcomes between people who received the real treatment and those who didn’t, helping them see whether any improvements were truly due to semaglutide.
Nearly 1,200 people with MASH and moderate to severe liver scarring are taking part in the study set to run for 240 weeks, or around four and a half years. At the start, study coordinators split the participants randomly into two groups: doctors would give one group weekly injections of semaglutide. The other group got a placebo, a shot that looked the same but had no active medicine. The researchers used a 2.4 mg dose of semaglutide, a standard dosage for people prescribed the drug for weight loss.
The trial was double blind, meaning that neither the participants nor the researchers knew who was receiving semaglutide or the placebo. This is intended to prevent bias and make the results trustworthy.
To ensure the two groups were as similar as possible, participants were also stratified based on factors like the stage of their liver disease, whether they had type 2 diabetes, and their geographic location. By carefully matching the control participants to the experimental group, the researchers were able to eliminate possible confounding variables. This, they hoped, would provide a clear picture of what the drug did.
The study planned to collect liver biopsies at the beginning of the trial, again at week 72 and then at 240 weeks. The team would use these biopsies to directly assess changes in liver tissue. They wanted to find out if semaglutide could resolve liver inflammation without increasing liver scarring and whether it could improve scarring without triggering more inflammation.
Big Results in Just 72 Weeks
After just 72 weeks, the difference between the two groups was clear. The ESSENCE team set about performing an interim analysis to see how semaglutide was performing versus the placebo.
As expected, the drug helped participants lose weight. Those who received semaglutide lost an average of 10.5% of their body weight, while the placebo group lost only about 2% . The improvements in liver health, however, stood out even more. Of the 768 people who received semaglutide, 483 showed decrease in liver fat accumulation and less inflammation, without additional liver scarring. Another 283 people also showed a reduction in their scarring
Patients didn’t just heal their livers; they got healthier overall, benefitting from thedrug’s known effects on diabetes and weight loss. Some had mild side effects, like nausea, but overall, the treatment was well tolerated.
The researchers tested a standard dose of 2.4 mg semaglutide weekly. This is in line with prescribing recommendations for weight loss. By using the standard dose, the researchers demonstrated that people already using semaglutide to lose weight will benefit from its effects on MASH.
This leads to an important question: were the liver improvements caused by semaglutide itself, or simply by the weight loss it caused? We know that taking steps to lose weight is the best way to stop MASH from getting worse.
From Trial to Treatment?
The full study will continue for several more years to track long-term effects, including whether patients will benefit from sustained improvements in liver health and whether semaglutide can prevent progression to cirrhosis or liver failure. But even at this early stage, the findings are gaining attention. Dr. Philip Newsome, one of the study’s lead investigators and a liver specialist at the University of Birmingham, called the results “a major breakthrough” and noted that the resolution of inflammation and reduction in scarring could change we treat MASHated in the future.
While it will be some time before doctors can prescribe semaglutide specifically for MASH, patients already using the drug will have another worry taken off their plate.
References
Sanyal, A. J., Newsome, P. N., Kliers, I., Østergaard, L. H., Long, M. T., Kjær, M. S., Cali, A. M. G., Bugianesi, E., Rinella, M. E., Roden, M., & Ratziu, V. (2025). Phase 3 Trial of Semaglutide in Metabolic Dysfunction—Associated Steatohepatitis. New England Journal of Medicine. https://doi.org/10.1056/nejmoa2413258
News Details. Novo Nordisk. Accessed June 5, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html
Weight-loss and diabetes drug semaglutide shows promise in fighting metabolic dysfunction-associated steatohepatitis and liver fibrosis. The once-weekly shot, marketed as Ozempic, Wegovy and Rybelsus, could be a breakthrough treatment for metabolic dysfunction-associated steatohepatitis (MASH), a serious and progressive form of fatty liver disease. So what’s the deal with semaglutide and MASH?
Published in April 2025 in the New England Journal of Medicine, an international team of metabolic medics says semaglutide could be the first drug-based therapy for MASH. Currently, this life-threatening liver disease has no approved pharmacological treatments, despite its well-known link to liver failure and liver cancer.
The results of this phase 3 clinical trial point to semaglutide as a useful tool to treat MASH with nearly 63% of participants experiencing reduced inflammation and approximately 37% showing less liver scarring.
MASH: The Silent Liver Disease on the Rise
MASH formerly known as non-alcoholic steatohepatitis (NASH) is a significant and increasingly common liver disease. The chronic liver condition develops when fat builds up in the liver, causing it to swell and scar. Over time, this damage can become so severe that the liver stops working altogether. MASH shares many of the same underlying drivers as obesity and type 2 diabetes. Current standards of care emphasize lifestyle changes aimed at weight loss. The idea is that if putting on weight correlates to more fat in the liver, not adding more should prevent MASH from getting worse. For many people, however, lifestyle changes aren’t enough.
This growing health issue has led to cross-border research efforts like the ESSENCE project (Essential Strategies to Stem the Epidemic of NASH in Canada and Europe). This international investigation focuses on finding better ways to treat MASH. Researchers looked at whether semaglutide, a drug already used to help people with type 2 diabetes and obesity, could also help people with MASH by reducing fat in the liver and giving it a chance to heal. They hypothesized that if semaglutide can support weight loss, it might also reduce the amount of fat stored in the liver. To test this idea, they conducted a randomized, placebo-controlled trial—the gold standard of clinical trials.
Methodology MASH Up
Researchers carried out a randomized, double-blind, placebo-controlled trial across 22 countries to test whether semaglutide could treat MASH. This study design allows scientists to directly compare outcomes between people who received the real treatment and those who didn’t, helping them see whether any improvements were truly due to semaglutide.
Nearly 1,200 people with MASH and moderate to severe liver scarring are taking part in the study set to run for 240 weeks, or around four and a half years. At the start, study coordinators split the participants randomly into two groups: doctors would give one group weekly injections of semaglutide. The other group got a placebo, a shot that looked the same but had no active medicine. The researchers used a 2.4 mg dose of semaglutide, a standard dosage for people prescribed the drug for weight loss.
The trial was double blind, meaning that neither the participants nor the researchers knew who was receiving semaglutide or the placebo. This is intended to prevent bias and make the results trustworthy.
To ensure the two groups were as similar as possible, participants were also stratified based on factors like the stage of their liver disease, whether they had type 2 diabetes, and their geographic location. By carefully matching the control participants to the experimental group, the researchers were able to eliminate possible confounding variables. This, they hoped, would provide a clear picture of what the drug did.
The study planned to collect liver biopsies at the beginning of the trial, again at week 72 and then at 240 weeks. The team would use these biopsies to directly assess changes in liver tissue. They wanted to find out if semaglutide could resolve liver inflammation without increasing liver scarring and whether it could improve scarring without triggering more inflammation.
Big Results in Just 72 Weeks
After just 72 weeks, the difference between the two groups was clear. The ESSENCE team set about performing an interim analysis to see how semaglutide was performing versus the placebo.
As expected, the drug helped participants lose weight. Those who received semaglutide lost an average of 10.5% of their body weight, while the placebo group lost only about 2% . The improvements in liver health, however, stood out even more. Of the 768 people who received semaglutide, 483 showed decrease in liver fat accumulation and less inflammation, without additional liver scarring. Another 283 people also showed a reduction in their scarring
Patients didn’t just heal their livers; they got healthier overall, benefitting from thedrug’s known effects on diabetes and weight loss. Some had mild side effects, like nausea, but overall, the treatment was well tolerated.
The researchers tested a standard dose of 2.4 mg semaglutide weekly. This is in line with prescribing recommendations for weight loss. By using the standard dose, the researchers demonstrated that people already using semaglutide to lose weight will benefit from its effects on MASH.
This leads to an important question: were the liver improvements caused by semaglutide itself, or simply by the weight loss it caused? We know that taking steps to lose weight is the best way to stop MASH from getting worse.
From Trial to Treatment?
The full study will continue for several more years to track long-term effects, including whether patients will benefit from sustained improvements in liver health and whether semaglutide can prevent progression to cirrhosis or liver failure. But even at this early stage, the findings are gaining attention. Dr. Philip Newsome, one of the study’s lead investigators and a liver specialist at the University of Birmingham, called the results “a major breakthrough” and noted that the resolution of inflammation and reduction in scarring could change we treat MASHated in the future.
While it will be some time before doctors can prescribe semaglutide specifically for MASH, patients already using the drug will have another worry taken off their plate.
References
Sanyal, A. J., Newsome, P. N., Kliers, I., Østergaard, L. H., Long, M. T., Kjær, M. S., Cali, A. M. G., Bugianesi, E., Rinella, M. E., Roden, M., & Ratziu, V. (2025). Phase 3 Trial of Semaglutide in Metabolic Dysfunction—Associated Steatohepatitis. New England Journal of Medicine. https://doi.org/10.1056/nejmoa2413258
News Details. Novo Nordisk. Accessed June 5, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html
