Arvanitakis Konstantinos, Koufakis Theocharis, Kalopitas Georgios, Papadakos Stavros P, Kotsa Kalliopi, Germanidis Georgios
Division of Gastroenterology and Hepatology, First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece; Basic and Translational Research Unit, Special Unit for Biomedical Research and Education, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54636, Thessaloniki, Greece.
Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece.
Diabetes Metab Syndr. 2024 Jan;18(1):102935. doi: 10.1016/j.dsx.2023.102935. Epub 2023 Dec 28.
Treatment of type 2 diabetes (T2D) in patients with compensated cirrhosis is challenging due to hypoglycemic risk, altered pharmacokinetics, and the lack of robust evidence on the risk/benefit ratio of various drugs. Suboptimal glycemic control accelerates the progression of cirrhosis, while the frequent coexistence of nonalcoholic fatty liver disease (NAFLD) with T2D highlights the need for a multifactorial therapeutic approach.
A literature search was performed in Medline, Google Scholar and Scopus databases till July 2023, using relevant keywords to extract studies regarding the management of T2D in patients with compensated cirrhosis.
Metformin, sodium-glucose co-transporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are promising treatment options for patients with T2D and compensated liver cirrhosis, offering good glycemic control with minimal risk of hypoglycemia, while their pleiotropic actions confer benefits on NAFLD and body weight, and decrease cardiorenal risk. Sulfonylureas cause hypoglycemia, thus should be avoided, while in specific studies, dipeptidyl peptidase-4 inhibitors have been correlated with increased risk of decompensation and variceal bleeding. Despite the benefits of thiazolidinediones in nonalcoholic steatohepatitis, concerns about edema and weight gain limit their use in compensated cirrhosis. Insulin does not exert hepatotoxic effects and can be administered safely in combination with other drugs; however, the risk of hypoglycemia should be considered.
The introduction of new hepatoprotective diabetes drugs into clinical practice, including tirzepatide, SGLT2i, and GLP-1 RA, sets the stage for future trials to investigate the ideal therapeutic regimen for people with T2D and compensated cirrhosis.
由于存在低血糖风险、药代动力学改变以及缺乏关于各种药物风险/效益比的有力证据,代偿期肝硬化患者的2型糖尿病(T2D)治疗具有挑战性。血糖控制不佳会加速肝硬化的进展,而非酒精性脂肪性肝病(NAFLD)与T2D的频繁共存凸显了多因素治疗方法的必要性。
截至2023年7月,在Medline、谷歌学术和Scopus数据库中进行了文献检索,使用相关关键词提取关于代偿期肝硬化患者T2D管理的研究。
二甲双胍、钠-葡萄糖协同转运蛋白2抑制剂(SGLT2i)和胰高血糖素样肽-1受体激动剂(GLP-1 RA)是T2D和代偿期肝硬化患者有前景的治疗选择,能实现良好的血糖控制且低血糖风险最小,同时它们的多效作用对NAFLD和体重有益,并降低心肾风险。磺脲类药物会导致低血糖,因此应避免使用,而在特定研究中,二肽基肽酶-4抑制剂与失代偿和静脉曲张出血风险增加相关。尽管噻唑烷二酮类药物对非酒精性脂肪性肝炎有益,但对水肿和体重增加的担忧限制了它们在代偿期肝硬化中的使用。胰岛素不会产生肝毒性作用,可以与其他药物安全联用;然而,应考虑低血糖风险。
将新的具有肝脏保护作用的糖尿病药物引入临床实践,包括替尔泊肽、SGLT2i和GLP-1 RA,为未来试验奠定了基础,以研究T2D和代偿期肝硬化患者的理想治疗方案。