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

There is accumulating evidence regarding the serious complications and mortality of NAFLD and its large burden on public healthcare systems (19) . However, optimal strategies for the prevention and treatment of NAFLD, particularly in the context of glucose metabolism, have not yet been fully investigated. Guidelines put forth by the AGA and the AASLD have recommended that TZD pioglitazone be used to treat patients with biopsy-proven, non-alcoholic steatohepatitis (NASH) (5, 20) . Therefore, we hypothesized that lobeglitazone, a novel TZD, could alleviate hepatic steatosis and improve hepatic function in T2D patients with CAP-proven NAFLD. In this multicenter, prospective, and exploratory trial, transient liver elastography assessed that a 24week treatment with lobeglitazone had significantly ameliorated hepatic steatosis in T2D patients with NAFLD, independent of glycemic control. Lobeglitazone treatment also resulted in improved glycemic profiles with reduced HbA1C and HOMAIR values, lipid profiles with increased HDL-C and decreased TG levels, and liver profiles with decreased AST, ALT, and γGTP levels. Multiple linear regression analyses further demonstrated that hepatic fat reduction by lobeglitazone was independently associated with baseline CAP values, metformin use, and chang- (22) reported that rosiglitazone ameliorates hepatic steatosis and aminotransferases, but not necroinflammation or fibrosis. A randomized clinical trial (RCT) conducted with 55 NASH patients who had impaired glucose tolerance or T2D, showed that pioglitazone treatment improves liver enzyme profiles and NASH histology, but not fibrosis (23) . Moreover, the trial also found that 73% of the pioglitazone-treated, compared with 24% of the placebo-treated, NASH patients showed improvement. Another RCT, conducted with 61 non-diabetic NASH patients, showed that a 12-month treatment with pioglitazone does not improve steatosis, but ameliorates hepatocellular injury and fibrosis, compared with placebo treatment on NASH patients (25) . However, the Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis (PIVENS) trial, which is a multicenter RCT of 247 non-diabetic patients with NASH, showed that 69% of pioglitazone-treated patients, compared with 31% of placebo-treated patients, achieved improvements in hepatosteatosis, as assessed by histology (P < 0.001) (24) .