Scientists compared two new medicines—resmetirom and semaglutide—to see how they treat a serious liver disease called MASH that develops from obesity and poor diet. Using mice that mimic human liver disease, they found both drugs helped improve the liver, but in different ways. Semaglutide worked mainly by reducing how much the mice ate, which also caused them to lose muscle. Resmetirom boosted the body’s energy burning without reducing muscle as much. Understanding these differences could help doctors choose the right medicine for each patient based on their individual needs.

The Quick Take

  • What they studied: How two different medicines treat a liver disease caused by obesity and poor diet, and whether they work the same way or differently in the body
  • Who participated: Male laboratory mice that were genetically modified to develop liver disease similar to humans. The mice were fed a Western-style diet (high in fat and processed foods) to make the disease worse
  • Key finding: Both medicines improved liver health, but they did it in completely different ways. Semaglutide reduced eating and caused muscle loss, while resmetirom boosted how many calories the body burned without affecting muscle as much
  • What it means for you: This research suggests that doctors may eventually be able to choose between these two medicines based on what’s most important for each patient—whether they want to focus on preserving muscle or reducing food intake. However, this is early research in mice, so more human studies are needed before these findings apply to people

The Research Details

Researchers used special mice that were genetically designed to develop a liver disease similar to what happens in obese humans. They fed these mice a Western diet (similar to fast food and processed foods that many people eat) for 6 weeks to create the disease. Then they gave some mice resmetirom and others semaglutide for 7 more weeks while continuing the unhealthy diet.

The scientists measured many things in the mice’s bodies: how much fat was in their livers, how much muscle they had, how much energy they burned, and what their liver tissue looked like under a microscope. They compared the results between the two treatment groups and a control group that got no medicine.

This type of study is called a ‘preclinical’ study because it uses animals to understand how medicines work before testing them in humans. The mice they used are considered a good model because they naturally develop liver disease similar to what happens in people with obesity.

Understanding how different medicines work helps doctors make better choices for patients. If two medicines both help the liver but affect the body differently, a doctor might pick one over the other depending on what the patient needs most. For example, someone worried about losing muscle might benefit from one medicine, while someone focused on eating less might do better with another. This research also helps scientists understand the different pathways in the body that can be targeted to treat liver disease.

This study was published in Scientific Reports, a well-respected scientific journal. The researchers used a mouse model that closely mimics human liver disease, which makes the findings more relevant to people. However, because this is animal research, the results may not work exactly the same way in humans. The study appears to be well-designed with careful measurements of multiple body systems, though the abstract doesn’t specify exactly how many mice were used in each group

What the Results Show

Both medicines significantly improved liver health in the mice. They both reduced the amount of fat stored in the liver and reduced scarring (fibrosis) of liver tissue, which is important because scarring is what turns a fatty liver into a more serious disease.

However, the two medicines achieved these improvements through different mechanisms. Semaglutide worked primarily by making the mice eat less food, which led to weight loss but also caused them to lose muscle tissue along with fat. Resmetirom, on the other hand, boosted the mice’s metabolism—essentially making their bodies burn more calories at rest—without significantly reducing how much they ate.

When researchers looked at the liver tissue under a microscope, resmetirom was particularly good at reducing fat accumulation in the liver cells. Semaglutide was particularly effective at reducing liver scarring and fibrosis, suggesting it may work better for more advanced liver disease.

These findings suggest that the two medicines target different biological pathways in the body to achieve similar improvements in liver health, which could explain why they have different side effects and benefits.

The study found that semaglutide reduced total energy expenditure (the amount of calories the body burns), while resmetirom actually increased energy expenditure. This is an important difference because it explains why the two drugs affect body composition differently. Semaglutide’s appetite-suppressing effect led to overall weight loss but also muscle loss, which can be a concern for some patients. Resmetirom’s metabolism-boosting effect preserved muscle better while still improving liver health.

Both resmetirom and semaglutide have shown benefits in human clinical trials for treating liver disease. This animal study confirms those findings and goes deeper by explaining how each medicine works differently. Previous research suggested semaglutide works mainly by reducing appetite and weight, which this study confirms. This is the first study to directly compare these two medicines side-by-side in the same disease model, providing new insights into their different mechanisms of action.

This study was conducted in mice, not humans, so the results may not translate exactly to people. The mice were genetically modified to develop liver disease, which may not perfectly match how the disease develops in humans through diet and lifestyle alone. The abstract doesn’t specify the exact number of mice used in each group, which makes it harder to assess the statistical power of the findings. Additionally, the study only looked at male mice, so it’s unclear whether these results would be the same in females. The mice were only treated for 7 weeks, so we don’t know what would happen with longer-term treatment

The Bottom Line

Based on this research, neither medicine can be recommended for human use yet—this is early-stage research. However, these findings suggest that future clinical trials should carefully monitor whether patients taking semaglutide experience muscle loss, and whether resmetirom’s metabolism-boosting effects translate to humans. Patients with liver disease should continue following their doctor’s current treatment plans and wait for human clinical trials to be completed. (Confidence level: Low, as this is animal research only)

This research is most relevant to people with obesity-related liver disease (MASH), their doctors, and pharmaceutical researchers developing new treatments. It’s also important for people considering semaglutide for weight loss, as it highlights the potential for muscle loss with this medication. People without liver disease don’t need to make any changes based on this research. This is preliminary research that will need human studies before it affects medical practice

This is basic research in mice, so it will likely take several years before these findings influence human treatment. Typically, promising animal studies lead to human clinical trials, which can take 3-5 years or more. Don’t expect changes to available treatments based on this single study

Want to Apply This Research?

  • If a user is taking either of these medications (or similar ones), they could track weekly body composition metrics: total weight, estimated muscle mass (if available through a smart scale), and energy levels. This would help them notice whether they’re losing muscle along with fat, which could indicate which medication might be better for them
  • Users could use the app to monitor their eating patterns and energy levels while on these medications. For semaglutide users, tracking appetite suppression and meal sizes would be valuable. For resmetirom users (if it becomes available), tracking energy levels and activity capacity would help assess the metabolism-boosting effects
  • Long-term tracking should include monthly measurements of weight, muscle mass percentage, energy expenditure (if available), and subjective measures like appetite, energy levels, and exercise capacity. Users should also track liver health markers if they have access to blood test results, particularly liver enzymes and fibrosis markers

This research was conducted in mice and has not been tested in humans. The findings do not yet apply to human medical treatment. Resmetirom and semaglutide are prescription medications that should only be used under direct medical supervision. If you have liver disease or are considering these medications, consult with your healthcare provider about the potential benefits and risks based on current human clinical evidence. This article is for educational purposes only and should not be used to make medical decisions. Always follow your doctor’s recommendations for treating liver disease