Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review

IF 3.4 3区医学 Q1 PEDIATRICS

Pediatric Drugs Pub Date : 2024-04-18 DOI:10.1007/s40272-024-00623-z

Sebastiano A. G. Lava, Craig Laurence, Alessandro Di Deo, Nicole Sekarski, Michael Burch, Oscar Della Pasqua

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Abstract

Introduction

In adults, sodium-glucose cotransporter type 2 inhibitors have revolutionised the treatment of type 2 diabetes mellitus, heart failure, and chronic kidney disease.

Objective

We aimed to review information on compassionate use, clinical pharmacology, efficacy, and safety of dapagliflozin and empagliflozin in children.

Methods

We conducted a systematic review of published clinical trials, case reports, and observational studies in Medline, Excerpta Medica, and Web of Science databases from inception to September 2023. For the two randomised controlled trials on type 2 diabetes mellitus (T2DM), we implemented a meta-analysis on the primary outcome (mean difference in glycosylated haemoglobin [HbA1c] between intervention and placebo groups). Review Manager (RevMan), version 5.4.1, was used for this purpose.

Results

Thirty-five articles (nine case reports, ten case series, one prospective non-controlled trial, four controlled randomised trials, two surveys, six pharmacokinetic studies, and three pharmacovigilance studies) were selected, in which 415 children were exposed to either dapagliflozin or empagliflozin: 189 diabetic patients (mean age 14.7 ± 2.9 years), 32 children with glycogen storage disease type Ib (GSD Ib), glucose-6-phosphatase catalytic subunit 3 (G6PC3) deficiency, or severe congenital neutropenia type 4 (8.5 ± 5.1 years), 47 children with kidney disease or heart failure (11.2 ± 6.1 years), 84 patients in pharmacokinetic studies (15.1 ± 2.3 years), and 63 patients in toxicological series. The effect of dapagliflozin and empagliflozin in T2DM was demonstrated by HbA1c reduction in two randomised trials among a total of 177 adolescents, with a mean HbA1c difference of -0.82% (95% confidence interval -1.34 to -0.29) as compared to placebo (no heterogeneity, I² = 0%). Dosage ranged between 5 and 20 mg (mean 11.4 ± 3.7) once daily for dapagliflozin and between 5 and 25 mg (mean 15.4 ± 7.4) once daily for empagliflozin. Among the paediatric cases of GSD Ib, empagliflozin 0.1–1.3 mg/kg/day improved neutropenia, infections, and gastrointestinal health. Dapagliflozin (mean dosage 6.9 ± 5.2 mg once daily) was well-tolerated in children with chronic kidney disease and heart failure. Side effects were generally mild, the most frequent being hypoglycaemia in children with GSD Ib (33% of patients) or T2DM (14% of patients) on concomitant hypoglycaemic drugs. Diabetic ketoacidosis is rare in children.

Conclusion

Early evidence suggests that dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.

Prospero Registration Number

CRD42023438162.

Abstract Image

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儿科用药中的达帕格列净和恩帕格列净：系统性综述

引言在成人中，钠-葡萄糖共转运体 2 型抑制剂彻底改变了 2 型糖尿病、心力衰竭和慢性肾病的治疗方法。方法我们对 Medline、Excerpta Medica 和 Web of Science 数据库中从开始到 2023 年 9 月已发表的临床试验、病例报告和观察性研究进行了系统综述。对于两项关于 2 型糖尿病（T2DM）的随机对照试验，我们对主要结果（干预组和安慰剂组之间糖化血红蛋白 [HbA1c] 的平均差异）进行了荟萃分析。结果选取了 35 篇文章（9 篇病例报告、10 篇系列病例、1 篇前瞻性非对照试验、4 篇对照随机试验、2 篇调查报告、6 篇药代动力学研究和 3 篇药物警戒研究），其中 415 名儿童接受了达帕格列净或恩格列净治疗：189 名糖尿病患者（平均年龄 14.7±2.9岁）、32名患有糖原贮积病Ib型（GSD Ib）、葡萄糖-6-磷酸酶催化亚基3（G6PC3）缺乏症或严重先天性中性粒细胞减少症4型的儿童（8.5±5.1岁）、47名患有肾脏疾病或心力衰竭的儿童（11.2±6.1岁）、84名参与药代动力学研究的患者（15.1±2.3岁）以及63名参与毒理学系列研究的患者。在两项随机试验中，共有177名青少年接受了达帕格列净和empagliflozin治疗，与安慰剂相比，HbA1c平均降低了-0.82%（95%置信区间-1.34至-0.29）（无异质性，I2 = 0%），证明了达帕格列净和empagliflozin治疗T2DM的效果。达帕格列净的用量为每天一次，每次 5 至 20 毫克（平均 11.4 ± 3.7）；恩帕格列净的用量为每天一次，每次 5 至 25 毫克（平均 15.4 ± 7.4）。在GSD Ib的儿科病例中，empagliflozin 0.1-1.3 mg/kg/天可改善中性粒细胞减少症、感染和胃肠道健康。患有慢性肾病和心力衰竭的儿童对达帕格列净（平均剂量为 6.9 ± 5.2 毫克，每天一次）的耐受性良好。副作用一般较轻，最常见的副作用是同时服用降糖药物的 GSD Ib（33% 的患者）或 T2DM（14% 的患者）患儿出现低血糖。结论早期证据表明，达帕格列净和恩格列净在儿童中的耐受性良好。目前仅有针对青少年糖尿病患者的临床药理依据。Prospero注册号CRD42023438162。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric Drugs PEDIATRICS-PHARMACOLOGY & PHARMACY

CiteScore

7.20

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Pediatric Drugs promotes the optimization and advancement of all aspects of pharmacotherapy for healthcare professionals interested in pediatric drug therapy (including vaccines). The program of review and original research articles provides healthcare decision makers with clinically applicable knowledge on issues relevant to drug therapy in all areas of neonatology and the care of children and adolescents. The Journal includes: -overviews of contentious or emerging issues. -comprehensive narrative reviews of topics relating to the effective and safe management of drug therapy through all stages of pediatric development. -practical reviews covering optimum drug management of specific clinical situations. -systematic reviews that collate empirical evidence to answer a specific research question, using explicit, systematic methods as outlined by the PRISMA statement. -Adis Drug Reviews of the properties and place in therapy of both newer and established drugs in the pediatric population. -original research articles reporting the results of well-designed studies with a strong link to clinical practice, such as clinical pharmacodynamic and pharmacokinetic studies, clinical trials, meta-analyses, outcomes research, and pharmacoeconomic and pharmacoepidemiological studies. Additional digital features (including animated abstracts, video abstracts, slide decks, audio slides, instructional videos, infographics, podcasts and animations) can be published with articles; these are designed to increase the visibility, readership and educational value of the journal’s content. In addition, articles published in Pediatric Drugs may be accompanied by plain language summaries to assist readers who have some knowledge of, but not in-depth expertise in, the area to understand important medical advances.