title: Lobeglitazone, a Novel Thiazolidinedione, Improves Non-Alcoholic Fatty Liver Disease in Type 2 Diabetes: Its Efficacy and Predictive Factors Related to Responsiveness.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yong Ho
authors.identifier: 0000-0002-6219-4942
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae Hyeon
authors.identifier: 0000-0001-5001-963X
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: So Ra
authors.identifier: 0000-0002-5778-370X
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.
authors.forename: Heung Yong
authors.identifier: 0000-0002-1841-2092
authors.initials: HY
authors.lastname: Jin
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Eun Jung
authors.identifier: 0000-0002-6108-7758
authors.initials: EJ
authors.lastname: Rhee
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Young Min
authors.identifier: 0000-0002-2331-6126
authors.initials: YM
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. bwanlee@yuhs.ac.
authors.forename: Byung Wan
authors.identifier: 0000-0002-9899-4992
authors.initials: BW
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004334:Drug Administration Schedule; D054459:Elasticity Imaging Techniques; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D016014:Linear Models; D008055:Lipids / Q000097:blood; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications*; D011446:Prospective Studies; D011743:Pyrimidines / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008055:Lipids; D008687:Metformin; D011743:Pyrimidines; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C546215:lobeglitazone
keywords: Non-Alcoholic Fatty Liver Disease; Thiazolidinedione; Transient Liver Elastography; Type 2 Diabetes