Effect of rosiglitazone on serum liver biochemistries in diabetic patients with normal and elevated baseline liver enzymes.

OBJECTIVES: Thiazolidinediones (TZD) are recommended to be used cautiously in diabetics with mild elevations in liver enzymes and not to be used in those with alanine aminotransferase>2.5 upper limit normal (ULN). However, studies are not adequate that evaluated the risk of TZD hepatotoxicity in diabetics with elevated liver enzymes. We conducted a study to test if diabetics with elevated liver enzymes have increased risk for hepatotoxicity from rosiglitazone (only TZD available on our formulary).
METHODS: This study consisted of two cohorts of patients prescribed rosiglitazone since January 2000. Cohort 1: 210 diabetics with elevated baseline liver enzymes (aspartate aminotransferase (AST)>40 IU/L and/or alanine aminotransferase (ALT)>35 IU/L) who received rosiglitazone, and cohort 2:628 diabetics with normal liver enzymes who received rosiglitazone. Elevations in liver biochemistries over a 12-month period after initiating rosiglitazone were characterized into mild to moderate or severe elevations and into "Hy's rule" based on published criteria.
RESULTS: Compared to cohort 2, patients in cohort 1 did not have higher incidence of mild to moderate (10% vs 6.6%, p=0.2) or severe elevations (0.9% vs 0.6%, p=0.9) in liver biochemistries. Similarly, the incidence of liver biochemistry abnormalities meeting the Hy's Rule was statistically not different between the two cohorts (0% vs 0.3%, p=0.9). The frequency of discontinuing rosiglitazone therapy during the follow-up was similar between cohorts 1 and 2 (8.6% vs 8.1%, p=1.0).
CONCLUSIONS: These results suggest that diabetics with elevated baseline liver enzymes do not have a higher risk of hepatotoxicity from rosiglitazone than those with normal enzymes.