Guo Nuojin, Shi Hekai, Zhang Hao, Wang Hua
Department of Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong District, Shanghai, 200120, China.
Department of Bariatric and Metabolic Surgery, Fudan University Affiliated Huadong Hospital, Shanghai, 200040, China.
Eur J Clin Pharmacol. 2023 Nov;79(11):1465-1474. doi: 10.1007/s00228-023-03561-w. Epub 2023 Sep 8.
The association between non-alcoholic fatty liver disease (NAFLD) and metabolic disorders, especially type-2 diabetes (T2DM), has been proven to be bidirectional. Hypoglycemic agents may be promising treatments for those disorders. However, there is currently no approved hypoglycemic therapy for NAFLD. In this review, we aimed to compare the efficacy and safety of twelve different hypoglycemic treatments in patients with NAFLD and T2DM.
We systematically screened randomized controlled trials (RCTs) published from March 2013 to March 2023 by searching PubMed, Embase, Medline, and Web of Science without any language restriction. We registered this project on the PROSPERO website: https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42023429701). All subsequent analyses were performed under the registered protocol. The mean difference (MD) and 95% confidence interval (95% CI) were adapted to evaluate the effect size of the treatment. The surface under the cumulative sorting curve (SUCRA) was used to rank the efficacy of the included treatments.
We included 19 trials involving 1212 patients in total. Insulin plus glucagon-like peptide-1 receptor agonist (GLP1RA) combination therapy was probably the most effective treatment for reducing weight and body mass index (BMI) (SUCRA: 0.93 and 1.00). Thiazolidinediones (TZD) were probably the most effective treatment for reducing glycosylated hemoglobin (HbA1c) and γ-glutamyltranspeptidase (γ-GGT) levels (SUCRA: 0.78 and 0.97). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) had the highest probability of presenting good therapeutic efficacy in reducing triglyceride (TG) levels (SUCRA: 0.72). The most common adverse reactions were gastrointestinal disorders, mainly after the administration of GLP1RA, and mild hypoglycemia, which was closely related to the use of insulin.
GLP1RA plus insulin combination therapy, GLP1RA, SGLT2i, and TZD may be the most effective therapeutic methods for patients with NAFLD and T2DM.
非酒精性脂肪性肝病（NAFLD）与代谢紊乱，尤其是2型糖尿病（T2DM）之间的关联已被证明是双向的。降糖药物可能是治疗这些疾病的有前景的方法。然而，目前尚无批准用于NAFLD的降糖疗法。在本综述中，我们旨在比较12种不同降糖治疗方法对NAFLD合并T2DM患者的疗效和安全性。
我们通过检索PubMed、Embase、Medline和Web of Science系统筛选了2013年3月至2023年3月发表的随机对照试验（RCT），无任何语言限制。我们在PROSPERO网站（https://www.crd.york.ac.uk/PROSPERO/，ID：CRD42023429701）上注册了该项目。所有后续分析均按照注册方案进行。采用平均差（MD）和95%置信区间（95%CI）评估治疗的效应大小。累积排序曲线下面积（SUCRA）用于对纳入治疗的疗效进行排序。
我们共纳入19项试验，涉及1212例患者。胰岛素加胰高血糖素样肽-1受体激动剂（GLP1RA）联合治疗可能是减轻体重和体重指数（BMI）最有效的治疗方法（SUCRA：0.93和1.00）。噻唑烷二酮类药物（TZD）可能是降低糖化血红蛋白（HbA1c）和γ-谷氨酰转肽酶（γ-GGT）水平最有效的治疗方法（SUCRA：0.78和0.97）。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）在降低甘油三酯（TG）水平方面呈现良好治疗效果的可能性最高（SUCRA：0.72）。最常见的不良反应是胃肠道疾病，主要发生在使用GLP1RA后，以及轻度低血糖，这与胰岛素的使用密切相关。
GLP1RA加胰岛素联合治疗、GLP1RA、SGLT2i和TZD可能是NAFLD合并T2DM患者最有效的治疗方法。
