Ezetimibe improves glucose metabolism by ameliorating hepatic function in Japanese patients with type 2 diabetes

Aims/Introduction: Several experimental studies have shown that ezetimibe improves steatosis and insulin resistance in the liver. This suggests that ezetimibe may improve glucose metabolism, as well as lipid metabolism, by inhibiting hepatic lipid accumulation. Therefore, we compared HbA1c levels after 3 months ezetimibe treatment with baseline levels in patients with type 2 diabetes and examined the factors associated with reductions in HbA1c following ezetimibe administration. Materials and Methods: Lipid profiles, hepatic function, and HbA1c were assessed before and after 3 months treatment with 10 mg/day ezetimibe in 96 patients with type 2 diabetes and hypercholesterolemia. Regression analysis was used to investigate associations between metabolite levels and the percentage change in HbA1c. Results: Low‐density lipoprotein–cholesterol was significantly lower after 3 months treatment compared with baseline, and HbA1c decreased in approximately 50% of patients. Univariate linear regression analyses showed that changes in HbA1c were significantly associated with serum alanine aminotransferase (ALT), the aspartate aminotransferase (AST)/ALT ratio, and age. Two‐tailed chi‐square tests revealed that serum ALT ≥35 IU/L and an AST/ALT ratio <1.0 were significantly associated with decreases in HbA1c following ezetimibe administration. Conclusions: The results of the present study indicate that ezetimibe may improve glucose metabolism. Serum ALT levels and the AST/ALT ratio were useful predictors of a glucose metabolism response to ezetimibe. This trial was registered with UMIN (no. UMIN000005307). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00147.x, 2011)