In clinical tests, involving more than 6,000 patients with type 2 diabetes who took rosiglitazone throughout North America and Europe, researchers found no hepatotoxic effects.
Researchers wondered whether rosiglitazone (Avandia tablet, GlaxoSmithKline) would act similar to another thiazolidine-dione, troglitazone (Rezulin, Warner-Lambert), which has been associated with idiosyncratic hepatic reactions leading to liver failure and death. They analyzed data from 13 double-blind clinical trials of rosiglitazone monotherapy and two ongoing, active-comparator clinical trials. No evidence of liver toxicity was observed either in monotherapy or in combination therapy for 5,006 patients.
The results aren’t unexpected, the researchers say, because rosiglitazone and troglitazone are markedly different in their biochemical and metabolic features and hepatic effects. Rosiglitazone is a PPAR-y agonist that is 100 times more effective than troglitazone. Both compounds have a thiazolinedione core, but they have different side chains. Unlike troglitazone, which has been shown to be directly toxic to cultured rat hepatocytes, rosiglitazone does not concentrate significantly in the liver, nor does it recirculate through the biliary system. The kidneys excrete 65% of the rosiglitazone generic. The researchers note that liver toxicity is unlikely to be a thiazoline-dione or PPAR-y agonist class effect.