Long-term use of pioglitazone appears to be safe and effective for patients with both nonalcoholic steatohepatitis (fatty liver disease) and prediabetes or type 2 diabetes mellitus. Results of a randomized, controlled trial are published in Annals of Internal Medicine.
Nonalcoholic fatty liver disease is reaching epidemic proportions and is the most common chronic liver condition in obese patients with prediabetes or type 2 diabetes. However, the condition is often overlooked and undertreated in these patients. This is a concern because patients with fatty liver disease and type 2 diabetes have an increased risk for vascular complications and are at the highest risk for cirrhosis and liver cancer. Pioglitazone is a medication in the class known as thiazolidinediones. Thiazolidinediones target insulin resistance and adipose tissue dysfunction or inflammation that promotes liver "liptoxicity" in fatty liver disease. For this reason, pioglitazone may be more helpful in treating patients with both fatty liver disease and prediabetes or type 2 diabetes.
Researchers randomly assigned 101 patients with prediabetes or type 2 diabetes and biopsy-proven fatty liver disease to either pioglitazone, 45 mg/d or placebo for 18 months, followed by an 18-month open-label phase with pioglitazone treatment. All patients were prescribed a low-calorie, weight-loss diet. After 3 years, patients were examined for a reduction in fatty liver disease activity without worsening of fibrosis and other histologic outcomes. They found that treatment with pioglitazone was associated with long-term metabolic and histologic improvements. These results suggest that fatty liver disease progression may be halted and the natural history of the disease may be modified with the use of pioglitazone in patients with prediabetes or type 2 diabetes.