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

Despite the rapidly increasing prevalence of non-alcoholic fatty liver disease (NAFLD) in type 2 diabetes (T2D), few treatment modalities are currently available. We investigated the hepatic effects of the novel thiazolidinedione (TZDs), lobeglitazone (Duvie) in T2D patients with NAFLD. We recruited drug-naïve or metformin-treated T2D patients with NAFLD to conduct a multicenter, prospective, open-label, exploratory clinical trial. Transient liver elastography (Fibroscan®; Echosens, Paris, France) with controlled attenuation parameter (CAP) was used to non-invasively quantify hepatic fat contents. Fifty patients with CAP values above 250 dB/m were treated once daily with 0.5 mg lobeglitazone for 24 weeks. The primary endpoint was a decline in CAP values, and secondary endpoints included changes in components of glycemic, lipid, and liver profiles. Lobeglitazone-treated patients showed significantly decreased CAP values (313.4 dB/m at baseline vs. 297.8 dB/m at 24 weeks; P = 0.016), regardless of glycemic control. Lobeglitazone improved HbA(1C) values (7.41% [57.5 mM] vs. 6.56% [48.2 mM]; P < 0.001), as well as the lipid and liver profiles of the treated patients. Moreover, multivariable linear regression analysis showed that hepatic fat reduction by lobeglitazone was independently associated with baseline values of CAP, liver stiffness, and liver enzymes, and metformin use. Lobeglitazone treatment reduced intrahepatic fat content, as assessed by transient liver elastography, and improved glycemic, liver, and lipid profiles in T2D patients with NAFLD. Further randomized controlled trials using liver histology as an end point are necessary to evaluate the efficacy of lobeglitazone for NAFLD treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02285205.ope