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

Am J Gastroenterol. 2005 Jun;100(6):1317-21. doi: 10.1111/j.1572-0241.2005.41690.x.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / blood
  • Alanine Transaminase / drug effects
  • Aspartate Aminotransferases / blood
  • Aspartate Aminotransferases / drug effects
  • Biomarkers / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Liver / chemistry*
  • Liver / drug effects
  • Male
  • Middle Aged
  • Retrospective Studies
  • Rosiglitazone
  • Severity of Illness Index
  • Thiazolidinediones / therapeutic use*
  • Transaminases / blood
  • Transaminases / drug effects*
  • Treatment Outcome


  • Biomarkers
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Transaminases
  • Aspartate Aminotransferases
  • Alanine Transaminase