AIM To assess the efficacy of exenatide (EXE) once weekly + dapagliflozin once daily (DAPA) versus each drug alone in reducing biomarkers of fatty liver/steatosis and fibrosis in a post hoc analysis of DURATION-8, a 104-week study in 695 patients with type 2 diabetes uncontrolled by metformin monotherapy. MATERIALS AND METHODS We evaluated the impact of the study treatments on non-invasive markers of hepatic steatosis (fatty liver index [FLI] and non-alcoholic fatty liver disease [NAFLD] liver fat score), fibrosis (fibrosis-4 index [FIB-4]) and severe fibrosis (NAFLD fibrosis score), along with liver enzymes and insulin resistance, at weeks 28 and 52. All outcomes in this analysis were exploratory, with nominal P values reported. RESULTS At week 28, biomarkers of fatty liver/steatosis and fibrosis were reduced from baseline in all treatment groups. At week 28, EXE once weekly + DAPA effects for decrease in FLI were stronger than those of EXE once weekly + placebo (PLB; -2.92, 95% confidence interval [CI] -5.11, -0.73; P = 0.0092) or DAPA+PLB (-2.77 [95% CI -4.93, -0.62]; P = 0.0119), and stronger than those of EXE once weekly + PLB at week 52 (-3.23 [95% CI -5.79, -0.68]; P = 0.0134). FIB-4 showed reduction versus baseline only in the EXE once weekly + DAPA group at both week 28 (-0.06 [95% CI -0.11, -0.01]; P = 0.0135) and week 52 (-0.05 [95% CI -0.09, -0.004]; P = 0.0308). CONCLUSIONS The EXE once weekly + DAPA combination showed stronger effects than EXE once weekly + PLB or DAPA + PLB in ameliorating markers of hepatic steatosis and fibrosis in patients with type 2 diabetes. Prospective trials are needed to validate these findings.

中文翻译：

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艾塞那肽和达格列净联合治疗可改善 2 型糖尿病患者的肝脂肪变性和纤维化标志物。

目的在对 DURATION-8 进行的一项 104 周研究中的 695二甲双胍单药治疗无法控制的 2 型糖尿病患者。材料和方法 我们评估了研究治疗对肝脂肪变性（脂肪肝指数 [FLI] 和非酒精性脂肪肝 [NAFLD] 肝脂肪评分）、纤维化（fibrosis-4 指数 [FIB- 4]）和严重纤维化（NAFLD 纤维化评分）以及肝酶和胰岛素抵抗，在第 28 周和第 52 周。该分析中的所有结果都是探索性的，报告了标称 P 值。结果在第 28 周，在所有治疗组中，脂肪肝/脂肪变性和纤维化的生物标志物均从基线降低。在第 28 周，EXE 每周一次 + DAPA 对降低 FLI 的效果强于 EXE 每周一次 + 安慰剂（PLB；-2.92，95% 置信区间 [CI] -5.11，-0.73；P = 0.0092）或 DAPA+ PLB (-2.77 [95% CI -4.93, -0.62]; P = 0.0119)，并且强于每周一次的 EXE + 第 52 周的 PLB (-3.23 [95% CI -5.79, -0.68]; P = 0.0134 ）。在第 28 周 (-0.06 [95% CI -0.11, -0.01]; P = 0.0135) 和第 52 周 (-0.05 [95% CI -0.09] , -0.004]；P = 0.0308)。结论 EXE 每周一次 + DAPA 组合在改善 2 型糖尿病患者肝脂肪变性和纤维化标志物方面显示出比 EXE 每周一次 + PLB 或 DAPA + PLB 更强的效果。