Clinical

Pioglitazone shows promise for nonalcoholic steatohepatitis treatment

Last Updated: 2006-11-29 17:00:08 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Treatment with pioglitazone appears to provide metabolic and histologic improvements in patients with nonalcoholic steatohepatitis, a disease for which no effective drug therapy currently exists, new research suggests.

Pioglitazone is an agent used to decrease insulin resistance and improve glucose and lipid metabolism in patients with type 2 diabetes. As such, the drug may also be beneficial for nonalcoholic steatohepatitis, a disease characterized by insulin resistance as well as by steatosis and necroinflammation.

The current proof-of-concept study, which is reported in The New England Journal of Medicine for November 30, involved 55 patients with confirmed nonalcoholic steatohepatitis who were randomized to receive a hypocaloric diet combined with pioglitazone (45 mg daily) or placebo for 6 months.

The pioglitazone intervention was associated with significant improvements in glycemic control and glucose tolerance, senior author Dr. Kenneth Cusi, from the University of Texas Health Science Center at San Antonio, and colleagues note.

Treatment with the drug also normalized liver aminotransferase levels, reduced hepatic fat content, and increased hepatic insulin sensitivity (p < 0.05 for all), the report indicates.

Hepatic histologic improvements seen with pioglitazone included reductions in steatosis, ballooning necrosis, and inflammation, the investigators state. While the drug significantly reduced necroinflammation compared with placebo, it did not have a significant anti-fibrosis effect.

Aside from fatigue and mild lower-extremity edema noted in one pioglitazone-treated subject, the drug was not associated with any adverse events.

In a related editorial, Dr. Arthur J. McCullough, from the Cleveland Clinic, comments that Dr. Cusi's team correctly characterizes the current research as a proof-of-concept study and notes that as a treatment for nonalcoholic steatohepatitis, thiazolidinediones are "promising but not ready for prime time."

He adds that "until the results of large, controlled studies of at least 1 or 2 years' duration are available, dietary modification, exercise, and treatment of coexisting conditions should be the preferred strategy for managing nonalcoholic steatohepatitis."

The study was supported in part by Takeda Pharmaceuticals, which markets pioglitazone as Actos.

N Engl J Med 2006;355:2297-2307, 2361-2363.