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‐analysis

Aims Glycogen storage disease type Ib (GSD‐Ib) is a rare genetic disorder causing neutropenia and neutrophil dysfunction in children. G‐CSF 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‐analysis assess its feasibility, efficacy and safety in paediatric GSD‐Ib patients. Methods Following the 2020 PRISMA guidelines, a systematic search was conducted in PubMed, Embase and Web of Science (2015–2025). The last search was performed on 16 May 2025. The inclusion criteria were patients <18 years with GSD‐Ib and neutropenia treated with empagliflozin. Eligible study types included randomized controlled trials (RCTs), observational studies and case series. Non‐English, pre‐2015 and non‐primary research were excluded. Bias was assessed using ROBINS‐I V2, and certainty via GRADE. Meta‐analyses 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. Results Six non‐randomized studies ( n = 177; 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 > 1.5) after empagliflozin treatment. Four studies had >80% resolution of neutropenia; all showed G‐CSF reduction or discontinuation. Adverse events were minimal; lactic acidosis was the most serious. Conclusions Empagliflozin shows promise in treating neutropenia in paediatric GSD‐Ib patients, with encouraging efficacy and safety. However, findings are limited by study design and heterogeneity. The majority of included studies were non‐randomized and rated as having a serious or critical risk of bias according to the ROBINS‐I 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‐AG, are needed to confirm empagliflozin's role as promising therapy in G‐CSF.