Scientists discovered that combining two medications—vildagliptin and sacubitril/valsartan—may help reduce dangerous pressure buildup in the liver caused by cirrhosis. Using rat models of liver disease, researchers found that these drugs work together to improve blood flow in the liver and reduce scarring. The medications appear to work by boosting natural protective molecules in the body while reducing harmful enzymes. This combination approach showed promise in two different types of liver disease models, suggesting it could become a new treatment option for people with advanced liver damage.

The Quick Take

  • What they studied: Whether two existing medications used for other conditions could help reduce pressure buildup in the liver and liver scarring in cirrhosis
  • Who participated: Laboratory rats with two different types of induced liver cirrhosis—one from a special diet and one from bile duct surgery
  • Key finding: Both medications alone reduced liver pressure and improved liver function, and when combined together, their benefits were even stronger in both disease models tested
  • What it means for you: This research is early-stage laboratory work in animals. While promising, these findings need human clinical trials before doctors could recommend these drugs for liver disease. People with cirrhosis should continue following their doctor’s current treatment plan.

The Research Details

Researchers created two different rat models of liver cirrhosis to mimic human liver disease. In the first model, rats ate a special diet lacking certain nutrients and high in fat to damage their livers. In the second model, surgeons tied off the bile duct (a tube that carries bile from the liver) to cause liver damage. Once the rats developed cirrhosis, researchers gave them either vildagliptin (a diabetes medication), sacubitril/valsartan (a heart disease medication), both drugs together, or no treatment. The scientists then measured multiple outcomes including liver pressure, enzyme activity, scarring, and blood vessel changes using various laboratory techniques.

Testing in animal models allows researchers to understand how drugs work at a cellular level before attempting human trials. Using two different disease models strengthens confidence that results aren’t specific to one method of causing liver damage. This approach helps identify promising drug combinations worth pursuing in human studies.

This is laboratory research in animals, which is an important first step but cannot be directly applied to humans. The study used established cirrhosis models and measured multiple relevant outcomes using validated scientific methods. However, animal studies don’t always translate to human effectiveness, and the actual sample sizes for each group weren’t specified in the abstract.

What the Results Show

Both medications significantly reduced the dangerous pressure that builds up in the liver (portal hypertension) in cirrhotic rats. The drugs achieved this by decreasing resistance to blood flow within the liver tissue itself, not by affecting overall blood pressure. When researchers combined both medications, the pressure-reducing effects were stronger than either drug alone. The medications worked by reducing an enzyme called soluble epoxide hydrolase (sEH) that normally breaks down protective molecules in the liver. By reducing this enzyme, the drugs allowed beneficial molecules called EETs to accumulate and improve blood vessel function.

The medications also reduced liver scarring (fibrosis) and prevented the activation of liver cells that cause scarring. They improved the health of the delicate blood vessels inside the liver and restored normal blood vessel markers. The drugs also reduced abnormal blood vessel growth and suppressed signaling pathways that promote liver damage. These improvements were seen in both types of cirrhosis models, suggesting the mechanism works across different causes of liver disease.

Previous research suggested that each drug class (diabetes medications and heart medications) might help with liver pressure separately. This study is novel because it’s the first to test them together and examine their combined effect on the specific molecular pathway (the sEH-EET system) that appears important in liver disease. The findings support the idea that combining drugs targeting different pathways might be more effective than single-drug approaches.

This research was conducted only in laboratory animals, not humans. The study doesn’t specify exact sample sizes for each treatment group. Animal livers don’t perfectly match human livers, so results may not translate directly to people. The study didn’t examine potential side effects or drug interactions in detail. Long-term effects and optimal dosing for humans remain unknown. These medications are approved for other conditions, but their safety and effectiveness specifically for liver disease in humans hasn’t been established.

The Bottom Line

This is preliminary laboratory research. Current evidence does not support using these medications specifically to treat liver cirrhosis in humans. People with cirrhosis should continue their prescribed treatments and discuss any new therapies with their hepatologist. Further research in human clinical trials would be needed before these drugs could be recommended for this purpose. Confidence level: Very low—this is animal research only.

Researchers studying liver disease and pharmaceutical companies developing cirrhosis treatments should pay attention to these findings. People with cirrhosis or their caregivers may find this interesting as a potential future direction, but it’s not actionable for current treatment. Gastroenterologists and hepatologists should monitor for future human trials.

This is basic research. If human trials begin soon, it would typically take 5-10 years before these medications could potentially become available for liver disease treatment, assuming they prove safe and effective in people.

Want to Apply This Research?

  • Users with cirrhosis could track liver-related symptoms (fatigue, abdominal swelling, appetite changes) weekly to monitor disease progression and treatment response, providing data to share with their doctor
  • Set reminders to take current liver medications as prescribed and schedule regular follow-up appointments with hepatologists to monitor liver function through blood tests
  • Log monthly check-ins documenting energy levels, abdominal symptoms, and any medication side effects; track lab results when available to identify trends in liver function over time

This article describes laboratory research in animals and should not be interpreted as medical advice. These findings do not currently support using vildagliptin or sacubitril/valsartan to treat liver cirrhosis in humans. Anyone with liver disease should work with their hepatologist or gastroenterologist regarding appropriate treatment. Do not start, stop, or change any medications without consulting your healthcare provider. This research is preliminary and requires human clinical trials before clinical application.