{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:09:52Z","timestamp":1791828592645,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"Aims<\/jats:title>Glycogen storage disease type Ib (GSD\u2010Ib) is a rare genetic disorder causing neutropenia and neutrophil dysfunction in children. G\u2010CSF has been the primary treatment, but emerging data support the potential of empagliflozin, an SGLT2 inhibitor, as a promising investigational option. This systematic review and meta\u2010analysis assess its feasibility, efficacy and safety in paediatric GSD\u2010Ib patients.<\/jats:p><\/jats:sec>Methods<\/jats:title>Following the 2020 PRISMA guidelines, a systematic search was conducted in PubMed, Embase and Web of Science (2015\u20132025). The last search was performed on 16 May 2025. The inclusion criteria were patients <18 years with GSD\u2010Ib and neutropenia treated with empagliflozin. Eligible study types included randomized controlled trials (RCTs), observational studies and case series. Non\u2010English, pre\u20102015 and non\u2010primary research were excluded. Bias was assessed using ROBINS\u2010I V2, and certainty via GRADE. Meta\u2010analyses used fixed or random effects depending on heterogeneity. The primary efficacy outcome was defined as resolution of neutropenia, and safety outcome included overall adverse events.<\/jats:p><\/jats:sec>Results<\/jats:title>Six non\u2010randomized studies (n<\/jats:italic>\u2009=\u2009177; 52% male; mean age 6.7) met the inclusion criteria. Two studies showed low risk of bias; three were critically biased. All reported improved neutrophil counts (ANC\u2009>\u20091.5) after empagliflozin treatment. Four studies had >80% resolution of neutropenia; all showed G\u2010CSF reduction or discontinuation. Adverse events were minimal; lactic acidosis was the most serious.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Empagliflozin shows promise in treating neutropenia in paediatric GSD\u2010Ib patients, with encouraging efficacy and safety. However, findings are limited by study design and heterogeneity. The majority of included studies were non\u2010randomized and rated as having a serious or critical risk of bias according to the ROBINS\u2010I tool. This substantially limits the reliability and interpretability of pooled outcomes. These results should therefore be viewed as preliminary and interpreted with caution. Further randomized trials, especially those measuring 1,5\u2010AG, are needed to confirm empagliflozin's role as promising therapy in G\u2010CSF.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bcp.70294","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T07:13:39Z","timestamp":1759216419000},"source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of empagliflozin for treating neutropenia and neutrophil dysfunction in paediatric patients with glycogen storage disease type Ib: A systematic review and meta\u2010analysis"],"prefix":"10.1002","author":[{"given":"Elizabeth","family":"Iwasyk","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy Pittsburgh United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Therapeutics University of Pittsburgh School 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7132-000X","authenticated-orcid":false,"given":"Alessio","family":"Provenzani","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Service Mediterranean Institute for Transplantation and Advanced Specialized Therapies (IRCCS ISMETT) Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"issue":"2","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.2174\/1566524024605798","article-title":"Type I glycogen storage diseases: disorders of the glucose\u20106\u2010phosphatase complex","volume":"2","author":"Chou JY","year":"2002","journal-title":"Curr Mol Med"},{"issue":"7","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1096\/fj.07-104851","article-title":"The glucose\u20106\u2010phosphate transporter is a phosphate\u2010linked 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