Long-Term Pioglitazone Use Effective in Patients with NASH and Prediabetes or Diabetes

By Atif Zaman, MD, MPH

Dr. Zaman is an associate editor with NEJM Journal Watch Gastroenterology, from which this story was adapted. Full coverage is available to subscribers at the link below.

Pioglitazone is associated with improved disease activity in patients with nonalcoholic steatohepatitis (NASH) plus prediabetes or diabetes, according to an industry-supported trial in the Annals of Internal Medicine.

Roughly 100 patients with biopsy-proven NASH and either prediabetes or type 2 diabetes were randomized to receive dietary counseling plus either daily pioglitazone or placebo for 18 months. Patients without resolution after 18 months could start or continue pioglitazone for another 18 months. The primary endpoint was reduction of at least 2 points on the nonalcoholic fatty liver disease activity score without worsening fibrosis.

At 18 months, patients receiving pioglitazone were significantly more likely than placebo recipients to achieve the primary endpoint (58% vs. 17%) and have NASH resolution (51% vs. 19%). Extending treatment to 36 months didn't further improve NASH histology. Adverse event rates were similar between the groups. However, weight gain was significantly greater in the pioglitazone group (mean difference, 2.5 kg).

Comment: Clinicians should consider pioglitazone for NASH in both diabetic and nondiabetic patients, especially those with fibrosis. However, its use needs to be balanced with the risks for weight gain, heart failure, and bone fractures.