Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials
Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetiro...
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2024-10-01
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| author | Hazem Ayesh Azizullah Beran Sajida Suhail Suhail Ayesh Kevin Niswender |
| author_facet | Hazem Ayesh Azizullah Beran Sajida Suhail Suhail Ayesh Kevin Niswender |
| author_sort | Hazem Ayesh |
| collection | DOAJ |
| description | Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ<sup>2</sup>, I<sup>2</sup>, and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD −18.41, 95% CI: −23.60 to −13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD −15.71, 95% CI: −23.30 to −8.13), AST (MD −12.28, 95% CI: −21.07 to −3.49), and GGT (MD −19.56, 95% CI: −34.68 to −4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2024-10-01 |
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| spelling | doaj-art-e4d6569d43f8464aaa31143968ecf0d82025-08-20T02:11:09ZengMDPI AGBiomedicines2227-90592024-10-011210232810.3390/biomedicines12102328Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical TrialsHazem Ayesh0Azizullah Beran1Sajida Suhail2Suhail Ayesh3Kevin Niswender4Deaconess Health System, Evansville, IN 47708, USADivision of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USAGene Medical Labs, Gaza 00972, PalestineGene Medical Labs, Gaza 00972, PalestineDepartment of Medicine, Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Nashville, TN 37232, USAIntroduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Metabolic-Dysfunction Associated Steatohepatitis (MASH) are linked to obesity, type 2 diabetes, and metabolic syndrome, increasing liver-related morbidity and cardiovascular risk. Recent therapies, including Resmetirom, FGF21 analogs, and GLP-1 agonists, have shown promise. This network meta-analysis evaluates their comparative efficacy and safety. Methods: A literature search was conducted across PubMed, Scopus, Web of Science, and Cochrane Library. Included clinical trials addressed MASLD or MASH with Resmetirom, FGF21 analogs, or GLP-1 agonists. Statistical analyses used a random-effects model, calculating mean differences (MD) and relative risks (RR), with heterogeneity assessed using τ<sup>2</sup>, I<sup>2</sup>, and Q statistics. Results: MASH resolution was significantly higher for FGF21 (RR 4.84, 95% CI: 2.59 to 9.03), Resmetirom showed the most significant reduction in MRI-PDFF (MD −18.41, 95% CI: −23.60 to −13.22) and >30% fat reduction (RR 3.56, 95% CI: 2.41 to 5.26). Resmetirom significantly reduced ALT (MD −15.71, 95% CI: −23.30 to −8.13), AST (MD −12.28, 95% CI: −21.07 to −3.49), and GGT (MD −19.56, 95% CI: −34.68 to −4.44). FGF21 and GLP-1 also reduced these markers. Adverse events were significantly higher with Resmetirom (RR 1.47, 95% CI: 1.24 to 1.74), while GLP-1 and FGF21 showed non-significant trends towards increased risk. Conclusions: Resmetirom and FGF21 show promise in treating MASLD and MASH, with Resmetirom particularly effective in reducing liver fat and improving liver enzymes. GLP-1 agonists also show benefits but to a lesser extent. Further long-term studies are needed to validate these findings and assess cost-effectiveness.https://www.mdpi.com/2227-9059/12/10/2328ResmetiromMASLDMASHFGF21GLP-1 |
| spellingShingle | Hazem Ayesh Azizullah Beran Sajida Suhail Suhail Ayesh Kevin Niswender Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials Biomedicines Resmetirom MASLD MASH FGF21 GLP-1 |
| title | Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials |
| title_full | Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials |
| title_fullStr | Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials |
| title_full_unstemmed | Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials |
| title_short | Comparative Analysis of Resmetirom vs. FGF21 Analogs vs. GLP-1 Agonists in MASLD and MASH: Network Meta-Analysis of Clinical Trials |
| title_sort | comparative analysis of resmetirom vs fgf21 analogs vs glp 1 agonists in masld and mash network meta analysis of clinical trials |
| topic | Resmetirom MASLD MASH FGF21 GLP-1 |
| url | https://www.mdpi.com/2227-9059/12/10/2328 |
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