J Korean Med Sci.  2017 Jan;32(1):60-69. 10.3346/jkms.2017.32.1.60.

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

• Lee YH
• Kim JH
• Kim SR
• Jin HY
• Rhee EJ
• Cho YM
• Lee BW

• KMID: 2417586
• DOI: http://doi.org/10.3346/jkms.2017.32.1.60

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 HbA1C 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 (Clinical trial No. NCT02285205).

Keyword

Non-Alcoholic Fatty Liver Disease; Thiazolidinedione; Type 2 Diabetes; Transient Liver Elastography

MeSH Terms

Elasticity Imaging Techniques
Humans
Linear Models
Liver
Metformin
Non-alcoholic Fatty Liver Disease*
Prevalence
Prospective Studies
Metformin

Figure

• 

  Fig. 1 A flow chart illustrates the disposition of subjects participating in the ELEGANCE study. ELEGANCE = Efficacy and Safety of the Use of LobEGlitazone in T2D PAtients with Non-alcoholiC Fatty LivEr Disease.

• 

  Fig. 2 Changes in CAP (A) and HbA1C (B) values following lobeglitazone treatment for 24 weeks and changes in CAP (C) and HbA1C (D) values according to patient responsiveness to lobeglitazone, as assessed by CAP, are shown. Values are presented as mean ± standard deviation (SD). CAP = controlled attenuation parameter, wk = week.

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