Effect of rosiglitazone on serum liver biochemistries in diabetic patients with normal and elevated baseline liver enzymes.
OBJECTIVE
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.
Chalasani
Naga
N
Department of Medicine, Indiana University School of Medicine; The Regenstrief Institute for Health Care, Indianapolis, Indiana 46202, USA.
Teal
Evgenia
E
Hall
Stephen D
SD
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000637:Transaminases / Q000097:blood / Q000187:drug effects*; D016896:Treatment Outcome
D015415:Biomarkers; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000637:Transaminases; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase