Rosiglitazone safe with some patients: study

By Megan Rauscher

NEW YORK (Reuters Health) – Diabetic patients with elevated
baseline liver enzymes are not at increased risk of
hepatotoxicity from treatment with the thiazolidinedione
rosiglitazone, results of a study suggest. “Rosiglitazone can
be safely used in diabetic patients with fatty liver disease,”
study leader Dr. Naga Chalasani told Reuters Health.

Although the second-generation thiazolidinediones –
rosiglitazone and pioglitazone — are “generally very safe from
a hepatic standpoint,” isolated reports of hepatotoxicity have
been reported, Dr. Chalasani, from Indiana University School of
Medicine in Indianapolis, pointed out.

It is currently recommended that rosiglitazone be used
cautiously in diabetics with mild elevations in liver enzymes
and that it not be used in those with alanine aminotransferase
greater than 2.5 the upper limit of normal, Dr. Chalasani and
colleagues explain in the June issue of the American Journal of
Gastroenterology.

However, they say, whether the risk of
thiazolidinedione-related hepatotoxicity is higher in diabetics
with elevated liver enzymes as opposed to normal liver enzymes
has not been adequately studied.

Dr. Chalasani’s team took a look back at the effect of
rosiglitazone on serum liver biochemistries in 210 diabetics
with elevated baseline liver enzymes (aspartate
aminotransferase greater than 40 IU/L and/or alanine
aminotransferase greater than 35 IU/L) and in 628 diabetics
with normal baseline liver enzymes.

Compared with diabetics with normal baseline liver enzymes,
those with elevated baseline liver enzymes did not have a
higher incidence of mild to moderate (10% vs. 6%) or severe
elevations in liver biochemistries (0.9% vs. 0.6%), the
investigators report.

“Our study,” Dr. Chalasani and colleagues conclude,
“provides important information about the safety of
rosiglitazone in diabetic patients with elevated baseline liver
enzymes.”

They also point out that “contrary to the manufacturers’
recommendation, rosiglitazone was prescribed for 15 patients
who had baseline liver enzymes 2.5 times the upper limit of
normal, and they all appeared to have tolerated the
rosiglitazone therapy with no evidence of hepatotoxicity.”

This observation, the authors say, should prompt further
study of the validity of the manufacturers’ recommendations
regarding rosiglitazone use in diabetics with elevated liver
enzymes.

Am J Gastroenterol 2005;100:1317-1321.