A three-year clinical study led by University of Florida Health researcher Kenneth Cusi, MD, has found that the diabetes treatment pioglitazone is safe and effective in certain patients who have nonalcoholic steatohepatitis (NASH), a chronic liver disease caused by a buildup of fat.
NASH—also known as “silent” liver disease—affects up to one-third of all patients with adult-onset diabetes in the United States, according to recent studies. Left unchecked, the disease can cause chronic inflammation leading to liver cancer or cirrhosis. It is the second-leading cause of liver transplants.
The early diagnosis and treatment of NASH is crucial for patients who are at greatest risk for the disease, usually obese individuals who also have prediabetes or type-2 diabetes (T2D), Cusi said. But until now, there was little urgency to diagnose NASH because there were no available medications.
The research group’s single-center clinical trial involved 101 NASH patients with prediabetes or T2D. The investigators found that pioglitazone reduced fatty liver disease activity in 58% of the subjects. In 51% of the subjects, the disease was reduced enough that it was no longer considered a threat to the liver.
“The exciting thing is that there is a generic drug that already prevents the onset of type-2 diabetes and cardiovascular disease in recent studies. Now, it can reduce disease from excess liver fat accumulation and liver inflammation, and halt fibrosis that leads to cirrhosis. This will have a lot of long-term benefits for many people with a medication that will be very affordable and is already being used to treat type-2 diabetes,” Cusi said.
The study results also have implications for people with prediabetes and NASH because fatty liver disease is a risk factor for T2D even in those who aren’t obese, Cusi added.
Federal regulators approved pioglitazone (Actos, Takeda) in 2000 to improve blood glucose control in adults with T2D, and a generic version of the drug was cleared in 2012. Still, the use of pioglitazone against liver disease will require supportive data from a large clinical trial, which could take seven years or more to complete, in addition to FDA approval.
The University of Florida researchers aren’t certain about how pioglitazone works against liver disease. Patients with NASH are insulin-resistant, meaning that their bodies do not respond normally to their own insulin. This defect promotes fat accumulation and inflammation in the liver. The researchers believe that pioglitazone provides molecular improvements in the liver and other tissues, such as fat. This may help the body’s response to insulin, making it insulin-sensitive again and restoring normal metabolism.
The findings were published in the Annals of Internal Medicine.
Source: Medical Xpress; June 21, 2016.