Abdel Monem Mona S, Adel Abdulmoneim, Abbassi Maggie M, Abdelaziz Doaa H, Hassany Mohamed, Raziky Maissa El, Sabry Nirmeen A
Department of Clinical Pharmacy, Faculty of Pharmacy, Cairo University, Egypt.
National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt.
Clin Res Hepatol Gastroenterol. 2025 Mar;49(3):102543. doi: 10.1016/j.clinre.2025.102543. Epub 2025 Jan 29.
Non-alcoholic steatohepatitis (NASH) is a serious end-stage spectrum of non-alcoholic fatty liver disease (NAFLD) with associated high risk of hepatic and extrahepatic complications. Several studies showed the significant beneficial effect of dapagliflozin on body composition, hepatic and metabolic parameters on NAFLD/NASH patients. The study aimed to investigate the efficacy and safety of dapagliflozin in both diabetic and non-diabetic biopsy-proven NASH patients; compared to pioglitazone.
This was a four-group, prospective, randomized, parallel, open label study in which 100 biopsy-proven NASH patients were selected, stratified to diabetics and non-diabetics and randomized with 1:1 allocation to either 30 mg pioglitazone or 10 mg dapagliflozin, once daily for 24 weeks. Histological evaluation, anthropometric measures, hepatic, metabolic biochemical markers, fibrosis non-invasive markers, quality of life (QOL) and medications adverse events were examined.
Dapagliflozin showed a comparable histological effect to pioglitazone in both diabetic and non-diabetic patients (P>0.05). As assessed by transient elastography, it also showed a comparable effect on liver fibrosis grade improvement from baseline in diabetics (P=0.287) versus a significant superiority in non-diabetics (P=0.018). Dapagliflozin showed a significant superiority in all anthropometric measures (P<0.001) and QOL (P<0.05) among both diabetics and non-diabetics. There was a significant interaction between interventions and diabetes status on change from baseline of hepatic and metabolic panel collectively (P=0.023) in favor to dapagliflozin among diabetics.
Compared to pioglitazone, dapagliflozin had a comparable effect histologically, superior effect biochemically among diabetics and superior effect on liver fibrosis, steatosis and insulin resistance among non-diabetics.
The study was registered on clinicaltrials.gov, identifier number NCT05254626.
非酒精性脂肪性肝炎（NASH）是一种严重的非酒精性脂肪性肝病（NAFLD）终末期疾病，伴有肝脏和肝外并发症的高风险。多项研究表明，达格列净对NAFLD/NASH患者的身体成分、肝脏和代谢参数具有显著的有益作用。本研究旨在探讨达格列净在经活检证实的糖尿病和非糖尿病NASH患者中的疗效和安全性；并与吡格列酮进行比较。
这是一项四组、前瞻性、随机、平行、开放标签研究，选取了100例经活检证实的NASH患者，分为糖尿病组和非糖尿病组，按1:1比例随机分配至30mg吡格列酮组或10mg达格列净组，每日一次，共治疗24周。对组织学评估、人体测量指标、肝脏和代谢生化标志物、纤维化非侵入性标志物、生活质量（QOL）和药物不良事件进行了检查。
在糖尿病和非糖尿病患者中，达格列净的组织学效果与吡格列酮相当（P>0.05）。通过瞬时弹性成像评估，它在糖尿病患者中对肝脏纤维化程度从基线改善的效果相当（P=0.287），而在非糖尿病患者中则具有显著优势（P=0.018）。达格列净在糖尿病和非糖尿病患者的所有人体测量指标（P<0.001）和生活质量（P<0.05）方面均显示出显著优势。在糖尿病患者中，干预措施与糖尿病状态之间在肝脏和代谢指标总体从基线变化方面存在显著交互作用（P=0.023），有利于达格列净。
与吡格列酮相比，达格列净在组织学上效果相当，在糖尿病患者中生化效果更优，在非糖尿病患者中对肝脏纤维化、脂肪变性和胰岛素抵抗的效果更优。
该研究已在clinicaltrials.gov上注册，标识符为NCT05254626。
