Treatment recommendations for glycogen storage disease type IB- associated neutropenia and neutrophil dysfunction with empagliflozin: Consensus from an international workshop.

Grünert, Sarah C;Derks, Terry G J;Mundy, Helen;Dalton, R Neil;Wortmann, Saskia B;et.al.
(2024) Molecular genetics and metabolism — Vol. 141, n° 3, p. 108144 (2024)

Files

Grunert2024.pdf
  • Open Access
  • Adobe PDF
  • 525.39 KB
Download

Details

Authors
  • Grünert, Sarah C
    Author
  • Derks, Terry G J
    Author
  • Mundy, Helen
    Author
  • Dalton, R Neil
    Author
  • Veiga da Cunha, MariaUCLouvain
    Author
  • Wortmann, Saskia B
    Author
Show more
Abstract
Glycogen storage disease type Ib (GSD Ib, biallelic variants in SLC37A4) is a rare disorder of glycogen metabolism complicated by neutropenia/neutrophil dysfunction. Since 2019, the SGLT2-inhibitor empagliflozin has provided a mechanism-based treatment option for the symptoms caused by neutropenia/neutrophil dysfunction (e.g. mucosal lesions, inflammatory bowel disease). Because of the rarity of GSD Ib, the published evidence on safety and efficacy of empagliflozin is still limited and does not allow to develop evidence-based guidelines. Here, an international group of experts provides 14 best practice consensus treatment recommendations based on expert practice and review of the published evidence. We recommend to start empagliflozin in all GSD Ib individuals with clinical or laboratory signs related to neutropenia/neutrophil dysfunction with a dose of 0.3-0.4 mg/kg/d given as a single dose in the morning. Treatment can be started in an outpatient setting. The dose should be adapted to the weight and in case of inadequate clinical treatment response or side effects. We strongly recommend to pause empagliflozin immediately in case of threatening dehydration and before planned longer surgeries. Discontinuation of G-CSF therapy should be attempted in all individuals. If available, 1,5-AG should be monitored. Individuals who have previously not tolerated starches should be encouraged to make a new attempt to introduce starch in their diet after initiation of empagliflozin treatment. We advise to monitor certain safety and efficacy parameters and recommend continuous, alternatively frequent glucose measurements during the introduction of empagliflozin. We provide specific recommendations for special circumstances like pregnancy and liver transplantation.
Affiliations

Citations

  • APA
  • Chicago
  • FWB

Grünert, S. C., Derks, T. G. J., Mundy, H., Dalton, R. N., Donadieu, J., Hofbauer, P., Jones, N., Uçar, S. K., LaFreniere, J., Contreras, E. L., Pendyal, S., Rossi, A., Schneider, B., Spiegel, R., Stepien, K. M., Wesol-Kucharska, D., Veiga da Cunha, M., & Wortmann, S. B. (2024). Treatment recommendations for glycogen storage disease type IB- associated neutropenia and neutrophil dysfunction with empagliflozin: Consensus from an international workshop. Molecular genetics and metabolism, 141(3), 108144. https://doi.org/10.1016/j.ymgme.2024.108144 (Original work published 2024)