Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review

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...

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Published in:Paediatric drugs 2024-05, Vol.26 (3), p.229-243
Main Authors: Lava, Sebastiano A. G., Laurence, Craig, Di Deo, Alessandro, Sekarski, Nicole, Burch, Michael, Della Pasqua, Oscar
Format: Article
Language:English
Subjects:
Adults
Antidiabetics
Case reports
CRD
CRD42023438162
Diabetes
Drug dosages
Ejection fraction
FDA approval
Glucose
Heart failure
Hemoglobin
Hypoglycemia
Internal Medicine
Kidney diseases
Medicine
Medicine & Public Health
Metabolism
Neutropenia
Oxidation
Pediatrics
Pharmacokinetics
Pharmacology
Pharmacotherapy
Pharmacovigilance
Systematic Review
Teenagers
Variance analysis
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Summary: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, I 2 = 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 dapa
ISSN:1174-5878
1179-2019
DOI:10.1007/s40272-024-00623-z