Pioglitazone improved NASH markers in patients with type 2 or prediabetes and NASH

Pioglitazone treatment was associated with improvements in nonalcoholic steatohepatitis (NASH) in patients with NASH and prediabetes or diabetes, a new study found.

The trial included 101 patients with prediabetes or type 2 diabetes and biopsy-proven NASH who were prescribed a hypocaloric diet and randomized to either 45 mg of pioglitazone per day or placebo for 18 months. After 18 months, pioglitazone was prescribed open label to all patients without histologic resolution of NASH. Results were published online by Annals of Internal Medicine on June 21.

The primary outcome was a reduction of at least 2 points in the nonalcoholic fatty liver disease score without worsening of fibrosis. By 18 months, this had occurred in significantly more of the pioglitazone patients than the placebo patients (58% vs. 17%; 95% CI for treatment difference, 23 to 59 percentage points). The pioglitazone group also had significantly more resolution of NASH (51% vs. 19%; 95% CI for difference, 13 to 51 percentage points). Pioglitazone was associated with significantly greater improvement in hepatic triglyceride content and adipose tissue, hepatic, and muscle insulin sensitivity and a nonsignificant reduction in the fibrosis score. The overall rate of adverse events did not differ between groups, although the pioglitazone group did have more weight gain (2.5 kg greater than placebo).

The results show long-term pioglitazone treatment to be safe and effective for such patients and may encourage early diagnosis and treatment, the study authors said. They called for larger, longer-term studies to replicate the results, especially in patients with more advanced fibrosis. The authors noted that this study aimed to identify patients who would respond to pioglitazone treatment, but no clinical or metabolic parameters were found to be effective for this purpose.

An accompanying editorial noted additional limitations to the findings, including that no additional histologic improvements were observed from extending pioglitazone treatment past 18 months and that the results were not separated for patients with prediabetes versus diabetes. Physicians should consider prescribing pioglitazone for patients with NASH and diabetes, “but the primary obstacle to the widespread use of pioglitazone remains its safety profile,” the editorialists said. “Thus, treatment should be considered for patients at the greatest risk (those with NASH and fibrosis) and should be balanced against the common risk for weight gain and the uncommon risks for fracture and heart failure.”

Annals of Internal Medicine's Diabetes Collection is online.