Top

Pediatric Drugs

Published in:

18-04-2024 | Dapagliflozin | Systematic Review

Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review

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

Published in: Pediatric Drugs | Issue 3/2024

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.

Available only for authorised users

Braunwald E. Gliflozins in the management of cardiovascular disease. N Engl J Med. 2022;386(21):2024–34. https://doi.org/10.1056/NEJMra2115011.CrossRefPubMed

McMurray JJV, Solomon SD, Inzucchi SE, Kober L, Kosiborod MN, Martinez FA, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. N Engl J Med. 2019;381(21):1995–2008. https://doi.org/10.1056/NEJMoa1911303.CrossRefPubMed

Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and renal outcomes with empagliflozin in heart failure. N Engl J Med. 2020;383(15):1413–24. https://doi.org/10.1056/NEJMoa2022190.CrossRefPubMed

McDonagh TA, Metra M, Adamo M, Gardner RS, Baumbach A, Böhm M, et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2022;24(1):4–131.CrossRefPubMed

Nassif ME, Windsor SL, Borlaug BA, Kitzman DW, Shah SJ, Tang F, et al. The SGLT2 inhibitor dapagliflozin in heart failure with preserved ejection fraction: a multicenter randomized trial. Nat Med. 2021;27(11):1954–60. https://doi.org/10.1038/s41591-021-01536-x.CrossRefPubMedPubMedCentral

Anker SD, Butler J, Filippatos G, Ferreira JP, Bocchi E, Bohm M, et al. Empagliflozin in heart failure with a preserved ejection fraction. N Engl J Med. 2021;385(16):1451–61. https://doi.org/10.1056/NEJMoa2107038.CrossRefPubMed

Solomon SD, McMurray JJV, Claggett B, de Boer RA, DeMets D, Hernandez AF, et al. Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction. N Engl J Med. 2022;387(12):1089–98. https://doi.org/10.1056/NEJMoa2206286.CrossRefPubMed

Desai AS, Lam CSP, McMurray JJV, Redfield MM. How to manage heart failure with preserved ejection fraction: practical guidance for clinicians. JACC Heart Fail. 2023;11(6):619–36. https://doi.org/10.1016/j.jchf.2023.03.011.CrossRefPubMed

Zelniker TA, Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors: JACC state-of-the-art review. J Am Coll Cardiol. 2020;75(4):422–34. https://doi.org/10.1016/j.jacc.2019.11.031.CrossRefPubMed

10.

Joshi SS, Singh T, Newby DE, Singh J. Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure. Heart. 2021;107(13):1032–8. https://doi.org/10.1136/heartjnl-2020-318060.CrossRefPubMed

11.

Katsiki N, Rizzo M, Mikhailidis DP. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors and uric acid: More good news! J Diabetes Complicat. 2023;37(7): 108510. https://doi.org/10.1016/j.jdiacomp.2023.108510.CrossRef

12.

Mora-Fernández C, Pérez A, Mollar A, Palau P, Amiguet M, de la Espriella R, et al. Short-term changes in klotho and FGF23 in heart failure with reduced ejection fraction—a substudy of the DAPA-VO2 study. Front Cardiovasc Med. 2023. https://doi.org/10.3389/fcvm.2023.1242108.CrossRefPubMedPubMedCentral

13.

Helmlinger G, Sokolov V, Peskov K, Hallow KM, Kosinsky Y, Voronova V, et al. Quantitative systems pharmacology: an exemplar model-building workflow with applications in cardiovascular, metabolic, and oncology drug development. CPT Pharmacomet Syst Pharmacol. 2019;8(6):380–95. https://doi.org/10.1002/psp4.12426.CrossRef

14.

Kula AJ. Considerations and possibilities for sodium-glucose cotransporter 2 inhibitors in pediatric CKD. Pediatr Nephrol. 2022;37(10):2267–76. https://doi.org/10.1007/s00467-022-05456-x.CrossRefPubMed

15.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. https://doi.org/10.1056/NEJMoa1504720.CrossRefPubMed

16.

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323–34. https://doi.org/10.1056/NEJMoa1515920.CrossRefPubMed

17.

Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–46. https://doi.org/10.1056/NEJMoa2024816.CrossRefPubMed

18.

Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–57. https://doi.org/10.1056/NEJMoa1611925.CrossRefPubMed

19.

Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–306. https://doi.org/10.1056/NEJMoa1811744.CrossRefPubMed

20.

Lava SA, Bianchetti MG, Simonetti GD. Salt intake in children and its consequences on blood pressure. Pediatr Nephrol. 2015;30(9):1389–96. https://doi.org/10.1007/s00467-014-2931-3.CrossRefPubMed

21.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372: n71. https://doi.org/10.1136/bmj.n71.CrossRefPubMedPubMedCentral

22.

Piffer A, Bianchetti MG, Leoni-Foglia C, Simonetti GD, Milani GP, Lava SAG. Vaptans for oedematous and hyponatraemic disorders in childhood: a systematic literature review. Br J Clin Pharmacol. 2022;88(10):4474–80. https://doi.org/10.1111/bcp.15367.CrossRefPubMed

23.

Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRefPubMed

24.

Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135. https://doi.org/10.1186/1471-2288-14-135.CrossRefPubMedPubMedCentral

25.

Galderisi A, Tamborlane W, Taylor SI, Attia N, Moretti C, Barbetti F. SGLT2i improves glycemic control in patients with congenital severe insulin resistance. Pediatrics. 2022. https://doi.org/10.1542/peds.2021-055671.CrossRefPubMed

26.

Tamborlane WV, Laffel LM, Shehadeh N, Isganaitis E, Van Name M, Ratnayake J, et al. Efficacy and safety of dapagliflozin in children and young adults with type 2 diabetes: a prospective, multicentre, randomised, parallel group, phase 3 study. Lancet Diabetes Endocrinol. 2022;10(5):341–50. https://doi.org/10.1016/S2213-8587(22)00052-3.CrossRefPubMedPubMedCentral

27.

Biester T, Aschemeier B, Fath M, Frey M, Scheerer MF, Kordonouri O, et al. Effects of dapagliflozin on insulin-requirement, glucose excretion and ss-hydroxybutyrate levels are not related to baseline HbA1c in youth with type 1 diabetes. Diabetes Obes Metab. 2017;19(11):1635–9. https://doi.org/10.1111/dom.12975.CrossRefPubMed

28.

Biester T, Muller I, von dem Berge T, Atlas E, Nimri R, Phillip M, et al. Add-on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: the DAPADream study. Diabetes Obes Metab. 2021;23(2):599–608. https://doi.org/10.1111/dom.14258.CrossRefPubMed

29.

Dos Santos SS, Ramaldes LA, Gabbay MAL, Moises RCS, Dib SA. Use of a sodium-glucose cotransporter 2 inhibitor, empagliflozin, in a patient with Rabson–Mendenhall syndrome. Horm Res Paediatr. 2021;94(7–8):313–6. https://doi.org/10.1159/000519613.CrossRefPubMed

30.

Candler T, McGregor D, Narayan K, Moudiotis C, Burren CP. Improvement in glycaemic parameters using SGLT-2 inhibitor and GLP-1 agonist in combination in an adolescent with diabetes mellitus and Prader–Willi syndrome: a case report. J Pediatr Endocrinol Metab. 2020;33(7):951–5. https://doi.org/10.1515/jpem-2019-0389.CrossRefPubMed

31.

Kuwabara R, Urakami T, Yoshida K, Morioka I. Case of type 2 diabetes possibly caused by excessive accumulation of visceral fat in a child born small-for-gestational age. J Diabetes Investig. 2020;11(5):1366–9. https://doi.org/10.1111/jdi.13246.CrossRefPubMedPubMedCentral

32.

Laffel LM, Danne T, Klingensmith GJ, Tamborlane WV, Willi S, Zeitler P, et al. Efficacy and safety of the SGLT2 inhibitor empagliflozin versus placebo and the DPP-4 inhibitor linagliptin versus placebo in young people with type 2 diabetes (DINAMO): a multicentre, randomised, double-blind, parallel group, phase 3 trial. Lancet Diabetes Endocrinol. 2023;11(3):169–81. https://doi.org/10.1016/S2213-8587(22)00387-4.CrossRefPubMedPubMedCentral

33.

Halligan RK, Dalton RN, Turner C, Lewis KA, Mundy HR. Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre. Orphanet J Rare Dis. 2022;17(1):195. https://doi.org/10.1186/s13023-022-02345-2.CrossRefPubMedPubMedCentral

34.

Kaczor M, Greczan M, Kierus K, Ehmke Vel Emczynska-Seliga E, Ciara E, Piatosa B, et al. Sodium-glucose cotransporter type 2 channel inhibitor: breakthrough in the treatment of neutropenia in patients with glycogen storage disease type 1b? JIMD Rep. 2022;63(3):199–206. https://doi.org/10.1002/jmd2.12278.CrossRefPubMedPubMedCentral

35.

Rossi A, Miele E, Fecarotta S, Veiga-da-Cunha M, Martinelli M, Mollica C, et al. Crohn disease-like enterocolitis remission after empagliflozin treatment in a child with glycogen storage disease type Ib: a case report. Ital J Pediatr. 2021;47(1):149. https://doi.org/10.1186/s13052-021-01100-w.CrossRefPubMedPubMedCentral

36.

Peeks F, Hoogeveen IJ, Feldbrugge RL, Burghard R, de Boer F, Fokkert-Wilts MJ, et al. A retrospective in-depth analysis of continuous glucose monitoring datasets for patients with hepatic glycogen storage disease: recommended outcome parameters for glucose management. J Inherit Metab Dis. 2021;44(5):1136–50. https://doi.org/10.1002/jimd.12383.CrossRefPubMedPubMedCentral

37.

Wortmann SB, Van Hove JLK, Derks TGJ, Chevalier N, Knight V, Koller A, et al. Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor. Blood. 2020;136(9):1033–43. https://doi.org/10.1182/blood.2019004465.CrossRefPubMedPubMedCentral

38.

Mikami M, Arai A, Mizumoto H. Empagliflozin ameliorated neutropenia in a girl with glycogen storage disease Ib. Pediatr Int. 2021;63(11):1394–6. https://doi.org/10.1111/ped.14629.CrossRefPubMed

39.

Contreras EL, D'Agosto M. View from inside: Nina, Glycogen storage disease warrior. J Inherit Metab Dis. 2020;43(4):653–56. https://doi.org/10.1002/jimd.12246.

40.

Tallis E, Karsenty CL, Grimes AB, Karam LB, Elsea SH, Sutton VR, et al. Untargeted metabolomic profiling in a patient with glycogen storage disease Ib receiving empagliflozin treatment. JIMD Rep. 2022;63(4):309–15. https://doi.org/10.1002/jmd2.12304.CrossRefPubMedPubMedCentral

41.

Hexner-Erlichman Z, Veiga-da-Cunha M, Zehavi Y, Vadasz Z, Sabag AD, Tatour S, et al. Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients. Front Pediatr. 2022;10:1071464. https://doi.org/10.3389/fped.2022.1071464.CrossRefPubMedPubMedCentral

42.

Guerra F, Gasperini S, Bonanomi S, Crescitelli V, Pretese R, Da Dalt L, et al. Finding balance between mature and immature neutrophils: the effects of empagliflozin in GSD-Ib. EJHaem. 2023;4(2):551–4. https://doi.org/10.1002/jha2.649.CrossRefPubMedPubMedCentral

43.

Murko S, Peschka M, Tsiakas K, Schulz-Jurgensen S, Herden U, Santer R. Liver transplantation in glycogen storage disease type Ib: the role of SGLT2 inhibitors. Mol Genet Metab Rep. 2023;35: 100977. https://doi.org/10.1016/j.ymgmr.2023.100977.CrossRefPubMedPubMedCentral

44.

Boulanger C, Stephenne X, Diederich J, Mounkoro P, Chevalier N, Ferster A, et al. Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: impact of a mutation in SGLT5. J Inherit Metab Dis. 2022;45(4):759–68. https://doi.org/10.1002/jimd.12509.CrossRefPubMedPubMedCentral

45.

Ledeczi Z, Pittner R, Krivan G, Kardon T, Legeza B. Empagliflozin restores neutropenia and neutrophil dysfunction in a young patient with severe congenital neutropenia type 4. J Allergy Clin Immunol Pract. 2023;11(1):344–6. https://doi.org/10.1016/j.jaip.2022.10.019. (e1).CrossRefPubMed

46.

Liu J, Cui J, Fang X, Chen J, Yan W, Shen Q, et al. Efficacy and safety of dapagliflozin in children with inherited proteinuric kidney disease: a pilot study. Kidney Int Rep. 2022;7(3):638–41. https://doi.org/10.1016/j.ekir.2021.12.019.CrossRefPubMed

47.

Newland DM, Law YM, Albers EL, Friedland-Little JM, Ahmed H, Kemna MS, et al. Early clinical experience with dapagliflozin in children with heart failure. Pediatr Cardiol. 2023;44(1):146–52. https://doi.org/10.1007/s00246-022-02983-0.CrossRefPubMed

48.

Busse D, Tang W, Scheerer M, Danne T, Biester T, Sokolov V, et al. Comparison of pharmacokinetics and the exposure-response relationship of dapagliflozin between adolescent/young adult and adult patients with type 1 diabetes mellitus. Br J Clin Pharmacol. 2019;85(8):1820–8. https://doi.org/10.1111/bcp.13981.CrossRefPubMedPubMedCentral

49.

Parkinson J, Tang W, Johansson CC, Boulton DW, Hamren B. Comparison of the exposure-response relationship of dapagliflozin in adult and paediatric patients with type 2 diabetes mellitus. Diabetes Obes Metab. 2016;18(7):685–92. https://doi.org/10.1111/dom.12647.CrossRefPubMed

50.

Tirucherai GS, LaCreta F, Ismat FA, Tang W, Boulton DW. Pharmacokinetics and pharmacodynamics of dapagliflozin in children and adolescents with type 2 diabetes mellitus. Diabetes Obes Metab. 2016;18(7):678–84. https://doi.org/10.1111/dom.12638.CrossRefPubMed

51.

Laffel LMB, Tamborlane WV, Yver A, Simons G, Wu J, Nock V, et al. Pharmacokinetic and pharmacodynamic profile of the sodium-glucose co-transporter-2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial. Diabet Med. 2018;35(8):1096–104. https://doi.org/10.1111/dme.13629.CrossRefPubMedPubMedCentral

52.

Penland RC, Melin J, Boulton DW, Tang W. Evaluation of the pharmacokinetics of dapagliflozin in patients with chronic kidney disease with or without type 2 diabetes mellitus. J Clin Pharmacol. 2023;63(5):551–9. https://doi.org/10.1002/jcph.2196.CrossRefPubMed

53.

Jo H, Pilla Reddy V, Parkinson J, Boulton DW, Tang W. Model-informed pediatric dose selection for dapagliflozin by incorporating developmental changes. CPT Pharmacomet Syst Pharmacol. 2021;10(2):108–18. https://doi.org/10.1002/psp4.12577.CrossRef

54.

Schaeffer SE, DesLauriers C, Spiller HA, Aleguas A, Baeza S, Ryan ML. Retrospective review of SGLT2 inhibitor exposures reported to 13 poison centers. Clin Toxicol (Phila). 2018;56(3):204–8. https://doi.org/10.1080/15563650.2017.1357824.CrossRefPubMed

55.

Frent I, Bucsa C, Leucuta D, Farcas A, Mogosan C. An investigation on the association between sodium glucose co-transporter 2 inhibitors use and acute pancreatitis: a VigiBase study. Pharmacoepidemiol Drug Saf. 2021;30(10):1428–40. https://doi.org/10.1002/pds.5313.CrossRefPubMed

56.

Katsuhara Y, Ikeda S. Correlations between SGLT-2 inhibitors and acute renal failure by signal detection using FAERS: stratified analysis for reporting country and concomitant drugs. Clin Drug Investig. 2021;41(3):235–43. https://doi.org/10.1007/s40261-021-01006-9.CrossRefPubMed

57.

Pereyra AM, Ramirez C, Roman R. Euglycemic ketosis in an adolescent with type 1 diabetes on insulin and dapaglifozin: case report. Rev Chil Pediatr. 2017;88(3):404–10. https://doi.org/10.4067/S0370-41062017000300015.CrossRef

58.

Grunert SC, Derks TGJ, Adrian K, Al-Thihli K, Ballhausen D, Bidiuk J, et al. Efficacy and safety of empagliflozin in glycogen storage disease type Ib: data from an international questionnaire. Genet Med. 2022;24(8):1781–8. https://doi.org/10.1016/j.gim.2022.04.001.CrossRefPubMed

59.

Grunert SC, Venema A, LaFreniere J, Schneider B, Contreras E, Wortmann SB, et al. Patient-reported outcomes on empagliflozin treatment in glycogen storage disease type Ib: an international questionnaire study. JIMD Rep. 2023;64(3):252–8. https://doi.org/10.1002/jmd2.12364.CrossRefPubMedPubMedCentral

60.

Kaczor M, Wesół-Kucharska D, Greczan M, Kierus K, Kałużny Ł, Duś-Żuchowska M, et al. Clinical characteristics and long-term outcomes of patients with glycogen storage disease type 1b: a retrospective multi-center experience in Poland. Pediatr Endocrinol Diabetes Metab. 2022;28(3):207–12. https://doi.org/10.5114/pedm.2022.116115.CrossRefPubMedPubMedCentral

61.

Grube PM, Beckett RD. Clinical studies of dapagliflozin in pediatric patients: a rapid review. Ann Pediatr Endocrinol Metab. 2022;27(4):265–72. https://doi.org/10.6065/apem.2244166.083.CrossRefPubMedPubMedCentral

62.

Tommerdahl KL, Nelson RG, Bjornstad P. Dapagliflozin in young people with type 2 diabetes. Lancet Diabetes Endocrinol. 2022;10(5):303–4. https://doi.org/10.1016/S2213-8587(22)00075-4.CrossRefPubMedPubMedCentral

63.

Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med. 1986;315(4):215–9. https://doi.org/10.1056/NEJM198607243150402.CrossRefPubMed

64.

Danne T, Garg S, Peters AL, Buse JB, Mathieu C, Pettus JH, et al. International consensus on risk management of diabetic ketoacidosis in patients with type 1 diabetes treated with sodium-glucose cotransporter (SGLT) inhibitors. Diabetes Care. 2019;42(6):1147–54. https://doi.org/10.2337/dc18-2316.CrossRefPubMedPubMedCentral

65.

Cirillo L, Ravaglia F, Errichiello C, Anders HJ, Romagnani P, Becherucci F. Expectations in children with glomerular diseases from SGLT2 inhibitors. Pediatr Nephrol. 2022;37(12):2997–3008. https://doi.org/10.1007/s00467-022-05504-6.CrossRefPubMed

66.

Zhao M, Sun S, Huang Z, Wang T, Tang H. Network meta-analysis of novel glucose-lowering drugs on risk of acute kidney injury. Clin J Am Soc Nephrol. 2020;16(1):70–8. https://doi.org/10.2215/CJN.11220720.CrossRefPubMedPubMedCentral

67.

Heerspink HJL, Cherney DZI. Clinical implications of an acute dip in eGFR after SGLT2 inhibitor initiation. Clin J Am Soc Nephrol. 2021;16(8):1278–80. https://doi.org/10.2215/CJN.02480221.CrossRefPubMedPubMedCentral

68.

Meoli M, Lava SAG, Bronz G, Goeggel-Simonetti B, Simonetti GD, Alberti I, et al. Eu- or hypoglycemic ketosis and ketoacidosis in children: a review. Pediatr Nephrol. 2023. https://doi.org/10.1007/s00467-023-06115-5.CrossRefPubMedPubMedCentral

69.

Bellanti F, Della PO. Modelling and simulation as research tools in paediatric drug development. Eur J Clin Pharmacol. 2011;67(Suppl 1):75–86. https://doi.org/10.1007/s00228-010-0974-3.CrossRefPubMedPubMedCentral

70.

Harnisch L, Shepard T, Pons G, Della PO. Modeling and simulation as a tool to bridge efficacy and safety data in special populations. CPT Pharmacom Syst Pharmacol. 2013;2(2): e28. https://doi.org/10.1038/psp.2013.6.CrossRef

Title: Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review
Authors: Sebastiano A. G. Lava
Craig Laurence
Alessandro Di Deo
Nicole Sekarski
Michael Burch
Oscar Della Pasqua
Publication date: 18-04-2024
Publisher: Springer International Publishing
Keywords: Dapagliflozin
Empagliflozin
Heart Failure
Ketoacidosis
Hypoglycemia
Published in: Pediatric Drugs / Issue 3/2024
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI: https://doi.org/10.1007/s40272-024-00623-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review

Abstract

Introduction

Objective

Methods

Results

Conclusion

Prospero Registration Number

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Objective

Methods

Results

Conclusion

Prospero Registration Number

Please log in to get access to this content

Other articles of this Issue 3/2024

The Effect of Polymorphisms and Other Biomarkers on Infliximab Exposure in Paediatric Inflammatory Bowel Disease: Development of a Population Pharmacokinetic Model

Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial

Existing and Emerging Targeted Therapies in Juvenile Psoriatic Arthritis: Challenges and Unmet Needs

Treatment Options for Alopecia Areata in Children and Adolescents

Improving Methylphenidate Titration in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): A Randomized Controlled Trial Using Placebo-Controlled Titration Implemented in Clinical Practice

Perforated appendicitis: room for improvement?