To increase our understanding of the effect of
thiazolidinediones, a new class of
antidiabetic drugs, on liver function as well as
glycemic control, we investigated liver function before, during, and
after treatment with
troglitazone and
pioglitazone. A total of 32 patients with
type 2 diabetes were studied.
Glycemic control and liver function were measured before, during, and after 4 to 12 weeks of treatment with
troglitazone or
pioglitazone.
Glycemic control was assessed by fasting levels of plasma
glucose,
hemoglobin A 1c , and serum
insulin, and liver function was assessed by asparatate
aminotransferase (AST),
alanine aminotransferase (ALT), and
gamma -glutamyl transpeptidase ( gamma-
GTP). Homeostasis model assessment for
insulin resistance was used as an index of
insulin resistance. During treatment with
troglitazone, fasting plasma
glucose and
hemoglobin A 1c levels and homeostasis model assessment for
insulin resistance were significantly decreased. Serum AST, ALT, and gamma-
GTP levels were significantly decreased during treatment (AST, -17.4%; ALT, -27.2%; gamma-
GTP, -47.9%) and returned to pretreatment levels after 4 weeks of withdrawal of the
drug. A similar tendency was observed during treatment with
pioglitazone (AST, -4.7%; ALT, -16.4%; gamma-
GTP, -30.8%). These data suggest that, in contrast to the deterioration of liver function reported in a small subset of patients treated with
troglitazone, treatment with
thiazolidinediones was associated with a decrease in serum
transaminases in most patients. The improvement in liver function parameters known to be associated with
fatty liver in the present study, together with an improvement in
fatty liver reported for another class of
insulin sensitizers,
biguanides, suggests that
thiazolidinediones may have a beneficial effect on
fatty liver.