司美格鲁肽联合恩格列净与单药治疗2型糖尿病非酒精性脂肪性肝病的疗效比较：一项随机临床试验的研究方案
Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.
作者信息
Lin Yu-Hao, Zhang Zhi-Jun, Zhong Jin-Qing, Wang Zhi-Yi, Peng Yi-Ting, Lin Yan-Mei, Zhang Huo-Ping, Tian Jian-Qing
机构信息
Department of Endocrinology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China.
Department of Laboratory Medicine, Xiamen Humanity Hospital, Fujian Medical University, Xiamen, Fujian, China.
出版信息
PLoS One. 2024 May 3;19(5):e0302155. doi: 10.1371/journal.pone.0302155. eCollection 2024.
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM.
METHODS
This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed.
DISCUSSION
This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM.
TRIAL REGISTRATION
This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).
背景
非酒精性脂肪性肝病（NAFLD）与2型糖尿病（T2DM）密切相关。生活方式干预仍然是NAFLD的首选治疗方式。胰高血糖素样肽（GLP-1）受体激动剂和钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂已被开发为新型降糖药物，可通过非胰岛素依赖的降糖作用改善脂肪肝。然而，探索GLP-1受体激动剂联合SGLT-2抑制剂治疗NAFLD和T2DM患者疗效的研究较少。因此，本随机对照试验旨在比较司美格鲁肽联合恩格列净与单独使用每种治疗方法对NAFLD和T2DM患者的疗效和安全性。
方法
这项为期52周的双盲、随机、平行组、活性对照试验评估了司美格鲁肽、恩格列净以及司美格鲁肽+恩格列净对105名符合条件的超重/肥胖NAFLD和T2DM患者的影响。主要结局指标将是从基线到第52周时受控衰减参数、游离脂肪酸和胰高血糖素的变化。次要终点包括肝脏硬度测量、肝酶、血糖、血脂水平、肾功能、电解质平衡、矿物质和骨代谢、细胞因子、高敏C反应蛋白、铁蛋白、人体测量指标、非酒精性脂肪性肝纤维化评分、纤维化4评分以及胰岛素抵抗的稳态模型评估的变化。此外，将进行意向性分析、中期分析和安全性分析。
讨论
这项双盲、随机临床试验采用多学科方法，旨在探索司美格鲁肽和恩格列净联合使用的协同效应。研究结果可为GLP-1受体激动剂和/或SGLT-2抑制剂在NAFLD和T2DM患者中的作用机制提供重要见解。
试验注册
本研究已在中国临床试验注册中心注册（ChiCTR2300070674）。
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