GLP-1RA治疗代谢相关脂肪性肝病疗效的Meta分析

Meta-Analysis of the Efficacy of GLP-1RA in the Treatment of Metabolic-Associated Fatty Liver Disease

摘要: 目的：系统评价胰高血糖素肽-1受体激动剂治疗(glucagon-like peptide-1 receptor agonist, GLP-1RA)代谢相关脂肪性肝病的疗效。方法：在中国知网(CNKI)、维普资讯中文期刊服务平台(VIP)、万方医学网、Cochrane Library、PubMed及Embase数据库中(截止2022年8月)进行全面系统检索，筛选符合纳入标准的随机对照试验(randomized control trail, RCT)，然后对纳入的文献进行资料提取及质量评价，最后运用RevMan 5.3软件进行Meta分析。结果：本研究共纳入13篇RCT，包含1208例患者。Meta分析结果显示：GLP-1RA相较于对照组可改善代谢相关脂肪性肝病患者的BMI (MD = 2.88, 95%CI: 1.16~4.60, P = 0.001)、体重(MD = 6.63, 95%CI: 3.51~9.75, P < 0.001)、胰岛素抵抗评价(MD = 0.22, 95%CI: 0.11~0.34, P = 0.0002)、甘油三酯(MD = 0.49, 95%CI: 0.17~0.82, P = 0.003)、低密度脂蛋白胆固醇(MD = 0.38, 95%CI: 0.17~0.59, P = 0.0005)、高密度脂蛋白胆固醇(MD = −0.15, 95%CI: −0.27~−0.03, P=0.01)、谷丙转氨酶(MD=13, 95%CI:9.62~16.39, P < 0.00001)、谷草转氨酶(MD = 7.95, 95%CI: 5.44~10.45, P < 0.00001)、脂联素(MD = −2.73, 95%CI: −4.21~−1.26, P = 0.0003)、肝脂肪含量(MD = 4.72, 95%CI: 1.82~7.62, P = 0.001)，而对空腹血糖(MD = 1.24, 95%CI: 0.16~2.32, P = 0.02)、餐后2小时血糖(MD = 1.91, 95%CI: −0.36~4.18, P = 0.10)、糖化血红蛋白(MD = 0.72, 95%CI: 0.03~1.41, P = 0.04)、总胆固醇(MD = 0.62, 95%CI: −0.14~1.38, P = 0.11)、高敏C反应蛋白(MD = 1.24, 95%CI: −0.18~2.66, P = 0.09)没有明显改善作用。结论：胰高血糖素肽-1受体激动剂可改善代谢相关脂肪性肝病患者的体重、胰岛素抵抗、血脂、肝酶及脂联素水平，但增加胃肠道不良反应。鉴于本次Meta分析纳入文献的样本量较小且文献质量一般，所以需要专门的大样本、多中心临床试验进行验证。

Abstract: Objective: To systematically evaluate the efficacy of human glucagon-like peptide-1 receptor agonist (GLP-1RA) in the treatment of metabolic-associated fatty liver disease. Methods: Comprehensive and systematic retrieval was conducted in CNKI, VIP, Wanfang Medical Network, Cochrane Library, PubMed and Embase databases (from inception to August 2022), and randomized controlled trials (RCTs) that met the inclusion criteria were selected. Then, data extraction and quality evaluation were performed for the included literature, and finally, a Meta-analysis was conducted by using RevMan 5.3 software. Results: A total of 13 RCTs were included in this study, including 1208 patients. The results of Meta-analysis showed: compared with the control group, GLP-1RA improved metabolic-associated fatty liver disease patients’ BMI (MD = 2.88, 95%CI: 1.16~4.60, P = 0.001), body weight (MD = 6.63, 95%CI: 3.51~9.75, P < 0.001), insulin resistance assessment (MD = 0.22, 95%CI:0.11~0.34, P = 0.0002), triglyceride (MD = 0.49, 95%CI:0.17~0.82, P = 0.003), low density lipoprotein cholesterol (MD = 0.38, 95%CI: 0.17~0.59, P = 0.0005), high density lipoprotein cholesterol (MD = −0.15, 95%CI: −0.27~−0.03, P = 0.01), alanine transaminase (MD = 13, 95%CI: 9.62~16.39, P < 0.00001), aspartate transaminase (MD = 7.95,95%CI: 5.44~10.45, P < 0.00001), adiponectin (MD = −2.73, 95%CI: −4.21~−1.26, P = 0.0003), liver fat content (MD = 4.72, 95%CI: 1.82~7.62, P = 0.001), but fasting plasma glucose (MD = 1.24, 95%CI: 0.16~2.32, P = 0.02), 2-hour plasma glucose (MD = 1.91, 95%CI: −0.36~4.18, P = 0.10), glycosylated hemoglobin (MD = 0.72, 95%CI: 0.03~1.41, P = 0.04), total cholesterol (MD = 0.62, 95%CI: −0.14~1.38, P = 0.11) and highly sensitive C-reactive protein (MD = 1.24, 95%CI: −0.18~2.66, P = 0.09) had no significant improvement. Conclusion: Glucagon-like peptide-1 receptor agonists can improve body weight, insulin resistance, lipid, liver enzymes and adiponectin levels in patients with metabolic-associated fatty liver disease, but they may increase the risk of gastrointestinal adverse reactions. In view of the small sample size and general quality of the literature included in this Meta-analysis, specialized large-sample, multi-center clinical trials are needed for verification.