OBJECTIVE To examine the effect of empagliflozin on liver fat content in individuals with and without type 2 diabetes (T2D) and the relationship between the decrease in liver fat and other metabolic actions of empagliflozin. RESEARCH DESIGN AND METHODS Thirty individuals with T2D and 27 without were randomly assigned to receive in double-blind fashion empagliflozin or matching placebo (2:1 ratio) for 12 weeks. Participants underwent 75-g oral glucose tolerance testing and measurement of liver fat content with MRS before therapy and at study end. Hepatic glucose production before the start of therapy was measured with 3-3H-glucose. RESULTS Empagliflozin caused an absolute reduction of 2.39% ± 0.79% in liver fat content compared with an increase of 0.91% ± 0.64% in participants receiving placebo (P < 0.007 with ANOVA). The decrease in liver fat was comparable in both individuals with diabetes and those without (2.75% ± 0.81% and 1.93% ± 0.78%, respectively; P = NS). The decrease in hepatic fat content caused by empagliflozin was strongly correlated with baseline liver fat content (r = −0.62; P < 0.001), decrease in body weight (r = 0.53; P < 0.001), and improvement in insulin sensitivity (r = −0.51; P < 0.001) but was not related to the decrease in fasting plasma glucose or HbA1c or the increase in hepatic glucose production. CONCLUSIONS Empagliflozin is effective in reducing liver fat content in individuals with and without T2D. The decrease in liver fat content is independent of the decrease in plasma glucose concentration and is strongly related to the decrease in body weight and improvement in insulin sensitivity.

中文翻译：

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恩格列净可减少糖尿病患者和非糖尿病患者的肝脏脂肪

目的 研究恩格列净对 2 型糖尿病 (T2D) 患者和非 2 型糖尿病 (T2D) 个体肝脏脂肪含量的影响，以及肝脏脂肪减少与恩格列净其他代谢作用之间的关系。研究设计和方法 30 名 T2D 患者和 27 名非 T2D 患者被随机分配接受双盲方式恩格列净或匹配安慰剂（2:1 比例）治疗 12 周。参与者在治疗前和研究结束时接受了 75 克口服葡萄糖耐量测试，并使用 MRS 测量肝脏脂肪含量。使用 3-3H-葡萄糖测量治疗开始前的肝葡萄糖产生。结果 恩格列净导致肝脏脂肪含量绝对减少 2.39% ± 0.79%，而接受安慰剂的参与者肝脏脂肪含量增加 0.91% ± 0.64%（方差分析 P < 0.007）。糖尿病患者和非糖尿病患者的肝脏脂肪减少量相当（分别为 2.75% ± 0.81% 和 1.93% ± 0.78%；P = NS）。恩格列净引起的肝脏脂肪含量降低与基线肝脏脂肪含量（r = -0.62；P < 0.001）、体重降低（r = 0.53；P < 0.001）和胰岛素敏感性改善密切相关（ r = -0.51；P < 0.001），但与空腹血糖或 HbA1c 的降低或肝葡萄糖生成的增加无关。结论恩格列净可有效降低患有和未患有 T2D 个体的肝脏脂肪含量。肝脏脂肪含量的降低与血浆葡萄糖浓度的降低无关，并且与体重的降低和胰岛素敏感性的改善密切相关。