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Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre
BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096769/ https://www.ncbi.nlm.nih.gov/pubmed/35549996 http://dx.doi.org/10.1186/s13023-022-02345-2 |
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author | Halligan, Rebecca K. Dalton, R. Neil Turner, Charles Lewis, Katherine A. Mundy, Helen R. |
author_facet | Halligan, Rebecca K. Dalton, R. Neil Turner, Charles Lewis, Katherine A. Mundy, Helen R. |
author_sort | Halligan, Rebecca K. |
collection | PubMed |
description | BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma. RESULTS: We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort. CONCLUSION: We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research. |
format | Online Article Text |
id | pubmed-9096769 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90967692022-05-12 Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre Halligan, Rebecca K. Dalton, R. Neil Turner, Charles Lewis, Katherine A. Mundy, Helen R. Orphanet J Rare Dis Research BACKGROUND: Glycogen storage disease type Ib (GSD Ib) is a severe disorder of carbohydrate metabolism due to bi-allelic variants in SLC37A4. It is associated with neutropaenia and neutrophil dysfunction, which has recently been attributed to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5AG6P) within neutrophils. Treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin, is a novel therapy that reduces 1,5-anhydroglucitol (1,5AG) in plasma. RESULTS: We report our experience in treating 8 paediatric GSD Ib patients with empagliflozin with a cumulative treatment time greater than 12 years. Treatment with a median dose of 5 mg (0.22 mg/kg height weight) of empagliflozin resulted in improvement in bowel health, growth, and laboratory parameters. Plasma 1,5AG levels reduced by a median of 78%. Baseline 1,5AG levels in our cohort were higher than in adult patients with GSD Ib. Hypoglycaemia on empagliflozin treatment occurred in 50% of our cohort. CONCLUSION: We report the largest single centre cohort of GSD Ib patients treated with empagliflozin to date. Treatment with SGLT2 inhibitors is a novel and favourable treatment option for neutropaenia and neutrophil dysfunction in GSD Ib. We suggest a low starting dose of empagliflozin with careful titration due to the risk of hypoglycaemia. The interpretation of 1,5AG levels and their role in treatment monitoring is yet to be established, and requires ongoing research. BioMed Central 2022-05-12 /pmc/articles/PMC9096769/ /pubmed/35549996 http://dx.doi.org/10.1186/s13023-022-02345-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Halligan, Rebecca K. Dalton, R. Neil Turner, Charles Lewis, Katherine A. Mundy, Helen R. Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title | Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title_full | Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title_fullStr | Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title_full_unstemmed | Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title_short | Understanding the role of SGLT2 inhibitors in glycogen storage disease type Ib: the experience of one UK centre |
title_sort | understanding the role of sglt2 inhibitors in glycogen storage disease type ib: the experience of one uk centre |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096769/ https://www.ncbi.nlm.nih.gov/pubmed/35549996 http://dx.doi.org/10.1186/s13023-022-02345-2 |
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