Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes, Obesity & Metabolism Pub Date : 2025-01-13 DOI:10.1111/dom.16198

Kiichi Hirayama, Masaya Koshizaka, Ryoichi Ishibashi, Mayumi Shoji, Takuro Horikoshi, Kenichi Sakurai, Koutaro Yokote

{"title":"Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub-analysis of a randomized controlled study.","authors":"Kiichi Hirayama, Masaya Koshizaka, Ryoichi Ishibashi, Mayumi Shoji, Takuro Horikoshi, Kenichi Sakurai, Koutaro Yokote","doi":"10.1111/dom.16198","DOIUrl":null,"url":null,"abstract":"Aims: To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis.Materials and methods: In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m2 and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated.Results: At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively).Conclusions: Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":" ","pages":""},"PeriodicalIF":5.4000,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/dom.16198","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Aims: To compare the effects of ipragliflozin, a sodium-dependent glucose transporter-2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi-centre, open-label, blinded-endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis.

Materials and methods: In total, 103 Japanese patients with type-2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m² and glycated haemoglobin level of 7%-10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non-alcoholic fatty liver disease-liver fat score (NAFLD-LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis-4 (FIB-4) index, were compared in the sub-analyses. The correlations between changes in each index and VFA were evaluated.

Results: At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (-9.24 ± 10.7 vs. -3.45 ± 11.8, p = 0.013), HSI (-1.45 ± 2.32 vs. -0.45 ± 1.87, p = 0.021), NAFLD-LFS (-0.70 ± 1.46 vs. -0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (-0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction (r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively).

Conclusions: Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early-stage liver disease associated with T2D.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

SGLT2抑制剂伊格拉列净和二甲双胍对肝脂肪变性和肝纤维化的影响：一项随机对照研究的亚分析

目的：为了比较钠依赖性葡萄糖转运蛋白-2抑制剂ipragliflozin和二甲双胍对内脏脂肪区（VFA）的影响，进行了一项前瞻性、多中心、开放标签、盲终点、随机对照研究。生成的数据用于检查伊普列净和二甲双胍对肝脂肪变性和肝纤维化指标的影响。材料与方法：103例日本2型糖尿病（T2D）患者，体重指数(BMI)≥22 kg/m2，糖化血红蛋白水平7% ~ 10%，随机给予伊普列净50 mg或二甲双胍1000 mg，疗程24周。在亚分析中比较肝脂肪变性指数、脂肪肝指数（FLI）、肝脂肪变性指数（HSI）、非酒精性脂肪肝-肝脂肪评分（NAFLD-LFS）、肝纤维化指数、AST /血小板比值指数（APRI）和纤维化-4指数（FIB-4）等参数。评价各指标变化与VFA的相关性。结果：在基线时，患者表现为中度肝脂肪变性，伊普拉列净组和二甲双胍组的FLI评分分别为52.9±26.6和57.8±29.0。在24周时，与二甲双胍相比，ipragliflozin改善了肝脏脂肪变性指数：FLI（-9.24±10.7比-3.45±11.8,p = 0.013）、HSI（-1.45±2.32比-0.45±1.87,p = 0.021）、NAFLD-LFS（-0.70±1.46比-0.04±0.98,p = 0.011）和肝纤维化指数：APRI（-0.110±0.323比0.033±0.181,p = 0.010）。在ipragliflozin组中，FLI和HSI的变化与VFA的减少相关(r = 0.340, p = 0.024；R = 0.367, p = 0.011)。结论：与二甲双胍相比，伊普列净可改善多发性肝脂肪变性和肝纤维化指标，提示伊普列净对早期T2D相关肝脏疾病具有潜在的肝保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.