{"title":"基于glp -1的治疗代谢功能障碍相关脂肪变性肝病和代谢功能障碍相关脂肪性肝炎的疗效：系统回顾和荟萃分析","authors":"Yahao Wang, Yue Zhou, Zhihong Wang, Yunzhi Ni, Gerald J Prud'homme, Qinghua Wang","doi":"10.1210/clinem/dgaf336","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.</p><p><strong>Methods: </strong>We searched PubMed, Embase and Cochrane Library database to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes (fibrosis-4, NFS, CK-18, procollagen III and liver stiffness) were evaluated. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model.</p><p><strong>Results: </strong>25 RCTs involving 2600 patients that used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with the retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning and lobular inflammation, but non-significantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver was observed.</p><p><strong>Conclusion: </strong>GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH.</p>","PeriodicalId":520805,"journal":{"name":"The Journal of clinical endocrinology and metabolism","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.\",\"authors\":\"Yahao Wang, Yue Zhou, Zhihong Wang, Yunzhi Ni, Gerald J Prud'homme, Qinghua Wang\",\"doi\":\"10.1210/clinem/dgaf336\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.</p><p><strong>Methods: </strong>We searched PubMed, Embase and Cochrane Library database to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes (fibrosis-4, NFS, CK-18, procollagen III and liver stiffness) were evaluated. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model.</p><p><strong>Results: </strong>25 RCTs involving 2600 patients that used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with the retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning and lobular inflammation, but non-significantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver was observed.</p><p><strong>Conclusion: </strong>GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH.</p>\",\"PeriodicalId\":520805,\"journal\":{\"name\":\"The Journal of clinical endocrinology and metabolism\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-06-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of clinical endocrinology and metabolism\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1210/clinem/dgaf336\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of clinical endocrinology and metabolism","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1210/clinem/dgaf336","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Efficacy of GLP-1-based Therapies on Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: A Systematic Review and Meta-Analysis.
Objective: New therapies are urgently needed for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). We conducted this systematic review and meta-analysis to evaluate the therapeutic effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on MASLD/MASH.
Methods: We searched PubMed, Embase and Cochrane Library database to identify randomized controlled trials (RCTs) that compared GLP-1RAs with placebo or active agents with respect to the efficacy in patients with MASLD/MASH. The effects of GLP-1RAs on liver fat content (LFC) by imaging, liver histology, serum liver enzymes, and noninvasive fibrosis indexes (fibrosis-4, NFS, CK-18, procollagen III and liver stiffness) were evaluated. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using a random-effect model.
Results: 25 RCTs involving 2600 patients that used GLP-1RAs including liraglutide, exenatide, dulaglutide, semaglutide, tirzepatide, efinopegdutide, survodutide and retatrutide were included. Overall, GLP-1RAs treatment for a median of 24 weeks demonstrated a significant reduction in LFC by 5.21%, with the retatrutide displaying the most obvious treatment effects. GLP-1RAs treatment induced significant histological improvements in steatosis, hepatocellular ballooning and lobular inflammation, but non-significantly improved fibrosis, with the evidence for tirzepatide more robust than that for semaglutide and liraglutide. GLP-1RAs treatment significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT) compared with control. GLP-1RAs also significantly improved liver stiffness, with semaglutide displaying the most obvious treatment effect. No drug-related adverse effects involving the liver was observed.
Conclusion: GLP-1RAs decreased liver fat deposition and improved histological steatosis, hepatocellular ballooning and lobular inflammation, without worsening of fibrosis in MASLD and MASH.
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