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Pioglitazone improves NASH, reduces fibrosis in type 2 diabetes

Pioglitazone effectively reduced nonalcoholic fatty liver disease activity score in patients with nonalcoholic steatohepatitis with and without type 2 diabetes, according to a recently published study. Pioglitazone also reduced liver fibrosis in patients with type 2 diabetes, but increased adipose tissue insulin sensitivity.

“These results suggest that pioglitazone may provide the same metabolic and histologic benefits to patients with NASH and prediabetes and to those with NASH and [type 2 diabetes],” Fernando Bril, MD, from the University of Florida, and colleagues wrote. “Greater improvements in resolution of NASH may suggest specific pioglitazone mechanisms in the [type 2 diabetes] population. While the effects on fibrosis appear to be similar in both groups, pioglitazone may contribute to halt the rapid progression observed in this group.”

The primary endpoint was a reduction in NAFLD activity score (NAS) by 2 points or more without worsened fibrosis.

Bril and colleagues enrolled 49 adult patients with prediabetes and 52 adults with type 2 diabetes and biopsy-proven NASH. Investigators randomly assigned patients to receive pioglitazone 30 mg per day or placebo for 18 months. Patients also received lifestyle counseling and followed a hypocaloric diet.

Those with type 2 diabetes were older (54 vs. 47 years; P = .001) and had more severe inflammation (1.8 vs. 1.5; P = .004) and fibrosis (1.2 vs. 0.8; P = .039) vs. patients with prediabetes. Patients were otherwise well-matched according to sex, BMI and total body fat.

Both patients with prediabetes and type 2 diabetes achieved similar rates of reduced NAS by 2 points or more (60% vs. 70%), which was comparable with the difference between pioglitazone treatment and placebo (48% vs. 46%). Those with type 2 diabetes, however, achieved significant resolution of NASH after pioglitazone therapy compared with placebo (60% vs. 16%; P = .002).

Similarly, patients with type 2 diabetes showed significant improvement in fibrosis after 18 months of pioglitazone treatment compared with placebo (–0.5 vs. 0.2; P = .042), whereas the treated prediabetes group did not.

In the prediabetes group, those who received pioglitazone had a significant reduction in fasting plasma insulin (–8 vs. –1 U/mL; P < .001) and a significant increase in plasma adiponectin (13.8 vs. –1.2 g/mL; P < .001) compared with the placebo group, whereas patients with type 2 diabetes showed a higher response in inflammation (P = .013) and ballooning (P = .006) compared with placebo.

Sixty-three patients completed 36 months of follow-up, 34 of whom received pioglitazone. All benefits that presented at 18 months of treatment with pioglitazone persisted after 36 months of therapy among the 18 patients with type-2 diabetes and 16 patients with prediabetes. – by Talitha Bennett

Disclosure: Bril reports no relevant financial disclosures. Please see the full study for the other authors’ relevant financial disclosures.