ArticleBlood2020
Treating neutropenia and neutrophil dysfunction in glycogen storage disease type Ib with an SGLT2 inhibitor.
Article in Blood, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 176 citations in OpenAlex.
- Safety of SGLT-2 inhibitors in patients with glycogen storage disease type Ib and their efficacy in treating disease-associated digestive symptoms and disorders.Acta diabetologica · 2026Pooled it
- Dapagliflozin and Empagliflozin in Paediatric Indications: A Systematic Review.Paediatric drugs · 2024Pooled it
- Short and long-term acceptability and efficacy of extended-release cornstarch in the hepatic glycogen storage diseases: results from the Glyde study.Orphanet journal of rare diseases · 2024Trial
- Effect of canagliflozin on white blood cell counts in patients with type 2 diabetes and heart failure: A subanalysis of the randomized CANDLE trial.Journal of diabetes investigation · 2022Trial
- Empagliflozin in GSD-Ib: Long-term safety and sustained recovery of neutrophil function including NET formation.Molecular genetics and metabolism reports · 2026Article
- Hospitalization, ICU admission, and mortality among diabetic patients with inflammatory bowel disease receiving SGLT-2 inhibitors: a retrospective cohort study from the global collaborative network.Annals of translational medicine · 2026Article
- Shifting Towards Empagliflozin First-Line Therapy in Glycogen Storage Disease Type Ib: A Nationwide Real-World Study.Journal of inherited metabolic disease · 2026Article
- SGLT2 inhibitors for kidney protection in children: expanding horizons beyond endocrinology.Pediatric nephrology (Berlin, Germany) · 2026Review
- Genetic testing guides therapy in children with refractory cytopenias.Haematologica · 2026Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- 1,5-Anhydroglucitol Aggravates Acute Liver Failure via the PPARα Signaling Pathway.Journal of clinical and translational hepatology · 2026Article
- Clinical Outcomes and Management in Late Diagnosed Siblings Affected With Attenuated GSD Ib.JIMD reports · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Novel murine model provides insights into early-onset of kidney disease in glycogen storage disease type Ib.Molecular genetics and metabolism · 2025Article
- Pathophysiology of the Neutropenia of GSDIb and G6PC3 Deficiency: Origin, Metabolism and Elimination of 1,5-Anhydroglucitol.Journal of inherited metabolic disease · 2025Review
- Clinical and Genetic Profile of 35 Patients with Glycogen Storage Disease Type 1b: A Comparative Analysis Before and During SGLT2 Inhibitor Therapy.Molecular diagnosis & therapy · 2025Article
- Spontaneous restoration of premature ovarian insufficiency and conception in a patient with glycogen storage disease type 1b managed with empagliflozin.Hormones (Athens, Greece) · 2025Article
- Potential Role of SGLT-2 Inhibitors in Improving Allograft Function and Reducing Rejection in Kidney Transplantation.Clinical transplantation · 2025Review
- Congenital Neutropenia Due toJournal of pharmacy & bioallied sciences · 2025Article
- [Efficacy and safety of empagliflozin in the treatment of glycogen storage disease-associated inflammatory bowel disease].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 8 institutions in 5 countries.
Funding
Abstract
Neutropenia and neutrophil dysfunction cause serious infections and inflammatory bowel disease in glycogen storage disease type Ib (GSD-Ib). Our discovery that accumulating 1,5-anhydroglucitol-6-phosphate (1,5AG6P) caused neutropenia in a glucose-6-phosphatase 3 (G6PC3)-deficient mouse model and in 2 rare diseases (GSD-Ib and G6PC3 deficiency) led us to repurpose the widely used antidiabetic drug empagliflozin, an inhibitor of the renal glucose cotransporter sodium glucose cotransporter 2 (SGLT2). Off-label use of empagliflozin in 4 GSD-Ib patients with incomplete response to granulocyte colony-stimulating factor (GCSF) treatment decreased serum 1,5AG and neutrophil 1,5AG6P levels within 1 month. Clinically, symptoms of frequent infections, mucosal lesions, and inflammatory bowel disease resolved, and no symptomatic hypoglycemia was observed. GCSF could be discontinued in 2 patients and tapered by 57% and 81%, respectively, in the other 2. The fluctuating neutrophil numbers in all patients were increased and stabilized. We further demonstrated improved neutrophil function: normal oxidative burst (in 3 of 3 patients tested), corrected protein glycosylation (2 of 2), and normal neutrophil chemotaxis (1 of 1), and bactericidal activity (1 of 1) under treatment. In summary, the glucose-lowering SGLT2 inhibitor empagliflozin, used for type 2 diabetes, was successfully repurposed for treating neutropenia and neutrophil dysfunction in the rare inherited metabolic disorder GSD-Ib without causing symptomatic hypoglycemia. We ascribe this to an improvement in neutrophil function resulting from the reduction of the intracellular concentration of 1,5AG6P.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.