Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review.

Autor: Lava SAG; Pediatric Cardiology Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland. webmaster@sebastianolava.ch.; Heart Failure and Transplantation, Department of Paediatric Cardiology, Great Ormond Street Hospital, London, UK. webmaster@sebastianolava.ch.; Clinical Pharmacology and Therapeutics Group, University College London, London, UK. webmaster@sebastianolava.ch.; Division of Clinical Pharmacology and Toxicology, Institute of Pharmacological Sciences of Southern Switzerland, Ente Ospedaliero Cantonale, Lugano, Switzerland. webmaster@sebastianolava.ch., Laurence C; Heart Failure and Transplantation, Department of Paediatric Cardiology, Great Ormond Street Hospital, London, UK., Di Deo A; Clinical Pharmacology and Therapeutics Group, University College London, London, UK., Sekarski N; Pediatric Cardiology Unit, Department of Pediatrics, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland., Burch M; Heart Failure and Transplantation, Department of Paediatric Cardiology, Great Ormond Street Hospital, London, UK., Della Pasqua O; Clinical Pharmacology and Therapeutics Group, University College London, London, UK.
Jazyk: angličtina
Zdroj: Paediatric drugs [Paediatr Drugs] 2024 May; Vol. 26 (3), pp. 229-243. Date of Electronic Publication: 2024 Apr 18.
DOI: 10.1007/s40272-024-00623-z
Abstrakt: 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 dapagliflozin and empagliflozin are well tolerated in children. A clinical pharmacology rationale currently exists only for adolescents with diabetes mellitus.
Prospero Registration Number: CRD42023438162.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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