Khaznadar Farah, Petrovic Ana, Khaznadar Omar, Roguljic Hrvoje, Bojanic Kristina, Kuna Roguljic Lucija, Siber Stjepan, Smolic Robert, Bilic-Curcic Ines, Wu George Y, Smolic Martina
Faculty of Dental Medicine and Health Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, Croatia.
J Clin Med. 2023 Oct 16;12(20):6561. doi: 10.3390/jcm12206561.
In the current modern era of unhealthy lifestyles, non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease and has become a serious global health problem. To date, there is no approved pharmacotherapy for the treatment of NAFLD, and necessary lifestyle changes such as weight loss, diet, and exercise are usually not sufficient to manage this disease. Patients with type 2 diabetes mellitus (T2DM) have a significantly higher risk of developing NAFLD and vice versa. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic agents that have recently been approved for two other indications: chronic kidney disease and heart failure in diabetics and non-diabetics. They are also emerging as promising new agents for NAFLD treatment, as they have shown beneficial effects on hepatic inflammation, steatosis, and fibrosis. Studies in animals have reported favorable effects of SGLT2 inhibitors, and studies in patients also found positive effects on body mass index (BMI), insulin resistance, glucose levels, liver enzymes, apoptosis, and transcription factors. There are some theories regarding how SGLT2 inhibitors affect the liver, but the exact mechanism is not yet fully understood. Therefore, biomarkers to evaluate underlying mechanisms of action of SGLT2 inhibitors on the liver have now been scrutinized to assess their potential as a future in-label therapy for NAFLD. In addition, finding suitable non-invasive biomarkers could be helpful in clinical practice for the early detection of NAFLD in patients. This is crucial for a positive disease outcome. The aim of this review is to provide an overview of the most recent findings on the effects of SGLT2 inhibitors on NAFLD biomarkers and the potential of SGLT2 inhibitors to successfully treat NAFLD.
在当前不健康生活方式盛行的现代社会，非酒精性脂肪性肝病（NAFLD）是最常见的肝脏疾病，已成为一个严重的全球健康问题。迄今为止，尚无获批用于治疗NAFLD的药物疗法，而诸如减肥、饮食和运动等必要的生活方式改变通常不足以控制这种疾病。2型糖尿病（T2DM）患者发生NAFLD的风险显著更高，反之亦然。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是一类抗糖尿病药物，最近已获批用于其他两个适应症：糖尿病患者和非糖尿病患者的慢性肾脏病和心力衰竭。它们也正成为治疗NAFLD的有前景的新型药物，因为它们已显示出对肝脏炎症、脂肪变性和纤维化有有益作用。动物研究报告了SGLT2抑制剂的有利作用，患者研究也发现其对体重指数（BMI）、胰岛素抵抗、血糖水平、肝酶、细胞凋亡和转录因子有积极影响。关于SGLT2抑制剂如何影响肝脏有一些理论，但确切机制尚未完全明确。因此，目前已对评估SGLT2抑制剂对肝脏作用潜在机制的生物标志物进行了仔细研究，以评估其作为NAFLD未来标签内治疗方法的潜力。此外，找到合适的非侵入性生物标志物可能有助于临床实践中早期检测患者的NAFLD。这对于良好的疾病预后至关重要。本综述的目的是概述SGLT2抑制剂对NAFLD生物标志物影响的最新研究结果以及SGLT2抑制剂成功治疗NAFLD的潜力。
