Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness

Lee, Yong-ho; Kim, Jae Hyeon; Kim, So Ra; Jin, Heung Yong; Rhee, Eun-Jung; Cho, Young Min; Lee, Byung-Wan

A previous study had suggested that better glycemic control affects improvement in fatty liver in T2D patients in response to drug treatment (31) . Thus, it could be argued that improvement of glycemic control alone might be responsible for reduced hepatic steatosis. To address this concern, we, in our current study, classified patients into two groups according to their lobeglitazone responsiveness. During the 24-week trial, two subjects, one in the responder group and the other in the non-responder group, received 2.0 mg glimepiride for rescue therapy. With the exception of these two subjects, participants showed improved glycemic control, as assessed by HbA1C and GA levels. Interestingly, although CAP values were only significantly reduced in the responder group, HbA1C values were significantly reduced in both the responder and non-responder groups. These data suggest that the reduction in hepatosteatosis is independent of the degree of glycemic control. There have been studies that investigate the pharmacologic mechanisms of TZDs in altering fat content and adipocytes (13) , and these mechanisms are thought to positively affect the distribution of fat mass and the proliferation of adipocytes resulting in weight gain (32) . Nevertheless, TZDs have also been shown to reduce liver fat content and enhance peripheral tissue glucose uptake (31) . In this regard, the negative side effects of TZDs on weight gain should be viewed in a balanced manner. Previous studies have shown that pioglitazone treatment increases body weight between 2.5 and 4.7 kg, depending on the study (23) (24) (25) . In our study, lobeglitazone treatment showed a lower increase in the average body weight of 1.4 kg (from 76.5 ± 11.1 kg to 77.9 ± 11.8 kg [P = 0.001]), which is similar to the weight gain, ranging from 0.89 to 1.48 kg, that was observed in other clinical trials using 0.5 mg/day lobeglitazone (15) (16) (17) .