FGF21 Analogues in Patients With Metabolic Diseases: Systematic Review and Meta-Analysis of Randomised Controlled Trials

IF 5.2 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Liver International Pub Date : 2025-02-03 DOI:10.1111/liv.70016

Panagiotis Theofilis, Evangelos Oikonomou, Paschalis Karakasis, Konstantinos Pamporis, Kyriakos Dimitriadis, Eleni Kokkou, Vaia Lambadiari, Gerasimos Siasos, Konstantinos Tsioufis, Dimitris Tousoulis

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Abstract

Background and Aims

Liver-related complications are frequent in patients with metabolic diseases, with limited treatment options currently available. This systematic review and meta-analysis aimed to assess the effect of fibroblast growth factor-21 (FGF21) analogues on hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases.

Methods

We conducted a systematic literature search in Pubmed, Scopus and Web of Science for randomised controlled trials (RCTs) assessing the effect of FGF21 analogues on hepatic steatosis evaluated by hepatic fat fraction (HFF), inflammation and fibrosis compared to placebo. Adverse events (AEs) were also recorded.

Results

Treatment with FGF21 analogues was associated with metabolic-associated steatohepatitis (MASH) resolution without fibrosis worsening (5 studies, risk ratio [RR] 4.40, 95% confidence interval [CI]: 2.41, 8.03, p < 0.001) and fibrosis improvement by 1 grade without MASH worsening (6 studies, RR 1.79, 95% CI: 1.24, 2.59, p = 0.002). FGF21 analogues significantly lowered HFF compared to placebo (6 studies, SMD -1.08, 95% CI: −1.28, −0.88, p < 0.001), while patients receiving FGF21 analogues were more likely to exhibit a reduction in HFF by 30% (10 studies, RR 4.08, 95% CI: 3.08, 5.40, p < 0.001) or 50% (6 studies, RR 10.43, 95% CI: 5.47, 19.87, p < 0.001). HFF normalisation (≤ 5%) was more frequently achieved with FGF21 analogues (6 studies, RR 14.58, 95% CI: 4.70, 45.18, p < 0.001). The results remained robust after sensitivity analyses. Serious AE and AE leading to drug discontinuation were similar in patients receiving FGF21 analogues or placebo.

Conclusions

FGF21 analogues can reduce hepatic steatosis, inflammation and fibrosis in patients with metabolic diseases, representing a possible treatment option for steatotic liver disease.

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代谢性疾病患者的FGF21类似物：随机对照试验的系统评价和荟萃分析

背景和目的：肝脏相关并发症在代谢性疾病患者中很常见，目前可用的治疗方案有限。本系统综述和荟萃分析旨在评估成纤维细胞生长因子-21 （FGF21）类似物对代谢性疾病患者肝脂肪变性、炎症和纤维化的影响。方法：我们在Pubmed， Scopus和Web of Science中进行了系统的文献检索，以随机对照试验（rct）评估FGF21类似物对肝脂肪变性的影响，通过肝脂肪分数（HFF），炎症和纤维化来评估与安慰剂相比。不良事件（ae）也被记录。结果：FGF21类似物治疗与代谢性脂肪性肝炎（MASH）的缓解相关，且无纤维化恶化（5项研究，风险比[RR] 4.40, 95%可信区间[CI]: 2.41, 8.03, p）。结论：FGF21类似物可减少代谢性疾病患者的肝脏脂肪变性、炎症和纤维化，是脂肪肝疾病的一种可能的治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.