Background: The aim of the present study was to compare the effects of gliclazide, liraglutide, and metformin in type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods: Eighty-seven subjects were randomized to receive liraglutide, metformin, or gliclazide for 24 weeks. Primary outcomes included HbA1c levels, intrahepatic fat (IHF) content, and liver function. Results: Both HbA1c levels and IHF content were reduced after treatment in all three groups. However, HbA1c levels were lower in the liraglutide-and metformin-treated groups than in the gliclazide-treated group, and reductions in IHF content were greater with liraglutide than with gliclazide. Liraglutide and metformin treatments reduced weight and improved liver function. Changes in IHF content were positively correlated with reductions in serum alanine aminotransferase and triglyceride levels, as well as weight. At 24 weeks, reductions in IHF content were greater in subjects with weight loss ≥5%, changes in waistline ≤0 cm (including decreases in waistline), HbA1c reductions ≥2.5%, and HbA1c levels <6.5%. Conclusions: In T2DM patients with NAFLD, compared with liraglutide and metformin, gliclazide resulted in less improvement in liver function, reductions in IHF content and HbA1c levels, and less weight loss; in addition, slightly better improvements were achieved with liraglutide than with metformin.
Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.
Aims/Introduction: To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non-alcoholic fatty liver disease. Materials and Methods: A total of 85 patients were randomly allocated to receive gliclazide (n = 27), liraglutide (n = 29) or metformin (n = 29) monotherapy for 24 weeks. Body composition was measured using dual-energy X-ray absorptiometry. Results: Liraglutide and metformin reduced total, trunk, limb, android and gynoid fat mass; this also led to weight reduction. However, gliclazide treatment produced no significant changes in weight or fat mass, likely because reductions in fat mass were concomitant with increases in lean tissue mass. Blood glucose concentrations and glycated hemoglobin levels improved in all treatment arms; levels of the latter were lower in patients treated with liraglutide and metformin. Serum alanine aminotransferase concentrations decreased in all treatment arms, whereas serum aspartate aminotransferase concentrations were reduced only by liraglutide and metformin. In all patients, weight loss and total, trunk, limb, and android fat mass reductions were positively correlated with decreases in serum alanine aminotransferase and aspartate aminotransferase levels, whereas reductions in waist circumference were positively correlated with lower serum alanine aminotransferase levels. Conclusions: Compared with gliclazide, liraglutide and metformin monotherapies result in greater weight loss, reductions in body fat mass, and better blood glucose control among type 2 diabetes mellitus patients with non-alcoholic fatty liver disease. Reductions in weight, fat mass and waist circumference favorably affect hepatic function.
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