Ayesh Hazem, Beran Azizullah, Suhail Sajida, Ayesh Suhail, Niswender Kevin
Deaconess Health System, Evansville, IN 47708, USA.
Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Biomedicines. 2024 Oct 14;12(10):2328. doi: 10.3390/biomedicines12102328.
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.
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, I, and Q statistics.
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.
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.
代谢功能障碍相关脂肪性肝病（MASLD）和代谢功能障碍相关脂肪性肝炎（MASH）与肥胖、2型糖尿病和代谢综合征相关，增加了肝脏相关发病率和心血管风险。包括Resmetirom、FGF21类似物和GLP-1激动剂在内的近期疗法已显示出前景。这项网状荟萃分析评估了它们的比较疗效和安全性。
在PubMed、Scopus、Web of Science和Cochrane图书馆进行文献检索。纳入的临床试验涉及使用Resmetirom、FGF21类似物或GLP-1激动剂治疗MASLD或MASH。统计分析采用随机效应模型，计算平均差（MD）和相对风险（RR），使用τ、I和Q统计量评估异质性。
FGF21使MASH缓解率显著更高（RR 4.84，95%置信区间：2.59至9.03），Resmetirom使MRI-PDFF降低最为显著（MD -18.41，95%置信区间：-23.60至-13.22）且脂肪减少>30%（RR 3.56，95%置信区间：2.41至5.26）。Resmetirom显著降低了ALT（MD -15.71，95%置信区间：-23.30至-8.13）、AST（MD -12.28，95%置信区间：-21.07至-3.49）和GGT（MD -19.56，95%置信区间：-34.68至-4.44）。FGF21和GLP-1也降低了这些指标。Resmetirom的不良事件显著更高（RR 1.47，95%置信区间：1.24至1.74），而GLP-1和FGF21显示出风险增加的非显著趋势。
Resmetirom和FGF21在治疗MASLD和MASH方面显示出前景，Resmetirom在减少肝脏脂肪和改善肝酶方面特别有效。GLP-1激动剂也显示出益处，但程度较小。需要进一步的长期研究来验证这些发现并评估成本效益。
