Factors associated with the risk of liver enzyme elevation in patients with type 2 diabetes treated with a thiazolidinedione.
OBJECTIVE
To characterize frequency of liver enzyme elevation in patients with type 2 diabetes mellitus receiving troglitazone.


METHODS
Retrospective study.


METHODS
Hospital-affiliated medical center.


METHODS
Two hundred ninety-one patients with type 2 diabetes mellitus.


METHODS
Data from patients with an average troglitazone exposure of 412.7 +/- 255.6 days were studied.


RESULTS
Enzyme elevations more than 1.5 times the upper limit of normal (ULN) occurred in 17 patients (5.8%) and more than 3-fold elevations in 6 (2.1%). The relationship among enzyme elevation events, demographic factors, duration of troglitazone exposure, frequency of monitoring, and concurrent drugs (limited to glucose and lipid-lowering agents) was assessed by multiple logistic regression. Age was an independent predictor of risk (p=0.009), and concurrent insulin therapy approached statistical significance (p=0.051) for 1.5-fold ULN elevation in liver enzymes. Age and concurrent therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were the only significant predictors of 3-fold ULN elevations (p=0.03 and p=0.04, respectively).


CONCLUSIONS
Several factors appear to increase the risk of enzyme elevation events in patients treated with troglitazone.
St Peter
J V
JV
Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA.
Neafus
K L
KL
Khan
M A
MA
Vessey
J T
JT
Lockheart
M S
MS
D000328:Adult; D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood* / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood* / Q000187:drug effects; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000201:enzymology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D013844:Thiazoles / Q000097:blood* / Q000494:pharmacology; D045162:Thiazolidinediones
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013844:Thiazoles; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase