Wu Qian, Liu Miaowen, Fang Zige, Li Chenxi, Zou Fang, Hu Lei, Zhang Wenxiong
Department of Endocrinology, The second affiliated hospital of Nanchang University, Nanchang, China.
Jiangxi Medical College, Nanchang University, Nanchang, China.
J Clin Pharm Ther. 2022 Mar;47(3):270-286. doi: 10.1111/jcpt.13521. Epub 2021 Sep 20.
As an oral hypoglycaemic drug that significantly reduces cardiovascular risk, empagliflozin is often used in patients with type 2 diabetes mellitus (T2DM). However, the dosage and administration of empagliflozin are still controversial clinically. To determine the most appropriate dose, we performed this network meta-analysis.
We identified randomized controlled trials (RCTs) about empagliflozin from eight databases. We analysed the pharmacodynamics, adverse effects (AEs), and pharmacokinetics of empagliflozin at different doses.
We identified 8264 articles, of which 23 RCTs with 10518 patients were included. Regarding haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), high-daily doses (10, 25, 50 mg) were significantly better than low doses (1, 2.5, 5 mg). For total AEs, there was a dose-response trend in which safety decreased with increasing doses. According to SUCRA sequencing, the order for lowering HbA1c was 25 > 50 > 10 > 5 > 1 mg, for lowering FPG was 50 > 25 > 10 > 5 > 2.5 > 1 mg and for safety was 1> 5 > 10 > 25> 2.5 > 50 mg. When considering HbA1c, FPG and total AEs, we performed a hierarchical cluster analysis and network meta-analysis to find that 25 mg performed best among different doses, which was more significant after long-term use (≥ 12 weeks). Pharmacokinetic parameters exhibited significant dose-response relationships.
High-daily doses (10, 25, 50 mg) had better efficacy than low doses (1, 2.5, 5 mg). When considering HbA1c, FPG and total AEs, 25 mg performed best among the different doses in patients with T2DM.
恩格列净作为一种能显著降低心血管风险的口服降糖药，常用于2型糖尿病（T2DM）患者。然而，恩格列净的剂量和用法在临床上仍存在争议。为确定最合适的剂量，我们进行了这项网状Meta分析。
我们从八个数据库中识别出关于恩格列净的随机对照试验（RCT）。我们分析了不同剂量恩格列净的药效学、不良反应（AE）和药代动力学。
我们识别出8264篇文章，其中纳入了23项RCT，涉及10518例患者。关于糖化血红蛋白（HbA1c）和空腹血糖（FPG），每日高剂量（10、25、50毫克）显著优于低剂量（1、2.5、5毫克）。对于总AE，存在剂量反应趋势，即安全性随剂量增加而降低。根据累积排序曲线下面积（SUCRA）排序，降低HbA1c的顺序为25＞50＞10＞5＞1毫克，降低FPG的顺序为50＞25＞10＞5＞2.5＞1毫克，安全性顺序为1＞5＞10＞25＞2.5＞50毫克。在考虑HbA1c、FPG和总AE时，我们进行了层次聚类分析和网状Meta分析，发现25毫克在不同剂量中表现最佳，长期使用（≥12周）后更显著。药代动力学参数呈现显著的剂量反应关系。
每日高剂量（10、25、50毫克）的疗效优于低剂量（1、2.5、5毫克）。在考虑HbA1c、FPG和总AE时，25毫克在T2DM患者的不同剂量中表现最佳。
