Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in children and young adults: a systematic review and meta-analysis.

IF 2.8 Q3 ENDOCRINOLOGY & METABOLISM Annals of Pediatric Endocrinology & Metabolism Pub Date : 2024-04-01 Epub Date: 2024-01-02 DOI:10.6065/apem.2346162.081
Lakshmi Nagendra, Deep Dutta, Harish Bukkasagar Girijashankar, Deepak Khandelwal, Tejal Lathia, Meha Sharma
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Abstract

Purpose: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap.

Methods: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events.

Results: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93-3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08-2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01-8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44-12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21-96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24-26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, β-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05-0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001).

Conclusion: SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

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钠葡萄糖共转运体-2 抑制剂在儿童和青少年中的安全性和耐受性:系统回顾和荟萃分析。
目的:在患有 2 型糖尿病 (T2DM)、1 型糖尿病 (T1DM) 和其他几种非糖尿病病症的儿童中,对葡萄糖钠协同转运体-2 抑制剂 (SGLT2i) 进行了评估。潜在的耐受性问题阻碍了我们在儿童糖尿病患者中常规使用 SGLT2i。迄今为止,还没有荟萃分析对儿童使用 SGLT2i 的安全性和耐受性进行评估。本系统综述和荟萃分析旨在填补这一知识空白:方法:在数据库中搜索了涉及干预组接受 SGLT2i 治疗的儿童的随机对照试验 (RCT)、病例对照和队列研究。主要结果是治疗突发不良事件(TAE)的发生率。次要结果是评估血糖疗效和严重不良事件(SAEs)、低血糖、酮症、生殖器或泌尿系统感染以及任何其他不良事件的发生:从初步筛选出的 27 篇文章中,分析了 4 项 RCT(258 名儿童)的数据。在 T2DM 患儿中,TAE [OR 1.77(95%CI:0.93-3.36);P=0.08;I2=0%], SAE [OR 0.45(95%CI:0.08-2.54);P=0.37;I2=0%], 酮症酸中毒 [OR 0.33(95%CI:0.01-8.37);P=0.50]、尿路感染[OR2.34(95%CI:0.44-12.50);P=0.32;I2=0%]和严重低血糖[OR4.47(95%CI:0.21-96.40);P=0.34]在SGLTi组和安慰剂组中具有可比性。与安慰剂相比,接受SGLTi治疗的T2DM儿童在24-26周时的HbA1C显著降低[MD -0.79%(95%CI:-1.33--0.26);P=0.004;I2=0%] 。在 T1DM 儿童中,SGLTi 组的ß-羟丁酸水平显著高于安慰剂组[MD 0.11mmol/L(95%CI:0.05-0.17);P=0.0005;I2=53%]。在 T1DM 患者中,两组患者均未出现 SAE、酮症酸中毒、严重低血糖等情况,SGLT2i 组患者的血糖维持时间明显长于安慰剂组(68%±6% vs. 50%±13%;P=0.0005;I2=53%):这项研究为我们提供了有关儿童和青少年使用 SGLT2i 的安全性的可靠数据。
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来源期刊
CiteScore
4.00
自引率
18.20%
发文量
59
审稿时长
24 weeks
期刊介绍: The Annals of Pediatric Endocrinology & Metabolism Journal is the official publication of the Korean Society of Pediatric Endocrinology. Its formal abbreviated title is “Ann Pediatr Endocrinol Metab”. It is a peer-reviewed open access journal of medicine published in English. The journal was launched in 1996 under the title of ‘Journal of Korean Society of Pediatric Endocrinology’ until 2011 (pISSN 1226-2242). Since 2012, the title is now changed to ‘Annals of Pediatric Endocrinology & Metabolism’. The Journal is published four times per year on the last day of March, June, September, and December. It is widely distributed for free to members of the Korean Society of Pediatric Endocrinology, medical schools, libraries, and academic institutions. The journal is indexed/tracked/covered by web sites of PubMed Central, PubMed, Emerging Sources Citation Index (ESCI), Scopus, EBSCO, EMBASE, KoreaMed, KoMCI, KCI, Science Central, DOI/CrossRef, Directory of Open Access Journals(DOAJ), and Google Scholar. The aims of Annals of Pediatric Endocrinology & Metabolism are to contribute to the advancements in the fields of pediatric endocrinology & metabolism through the scientific reviews and interchange of all of pediatric endocrinology and metabolism. It aims to reflect the latest clinical, translational, and basic research trends from worldwide valuable achievements. In addition, genome research, epidemiology, public education and clinical practice guidelines in each country are welcomed for publication. The Journal particularly focuses on research conducted with Asian-Pacific children whose genetic and environmental backgrounds are different from those of the Western. Area of specific interest include the following : Growth, puberty, glucose metabolism including diabetes mellitus, obesity, nutrition, disorders of sexual development, pituitary, thyroid, parathyroid, adrenal cortex, bone or other endocrine and metabolic disorders from infancy through adolescence.
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