{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:37:21Z","timestamp":1785836241653,"version":"3.56.0"},"reference-count":32,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T00:00:00Z","timestamp":1777766400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Neutrophil dysfunction and neutropenia are burdensome findings in glycogen storage disease type Ib (GSDIb). Treatment with granulocyte\u2010colony stimulating factor (G\u2010CSF) often corrects neutropenia but fails to improve clinical symptoms like inflammatory bowel disease (IBD). Recently, empagliflozin (EMPA) was shown to correct the neutrophil dysfunction and its clinical consequences. It is increasingly used as first\u2010line monotherapy, but long\u2010term, real\u2010world data are lacking. This nation\u2010wide retrospective study investigated 42 GSD1b patients (36 children) treated with EMPA as first\u2010line monotherapy and compared them with those receiving combination therapy with G\u2010CSF and treatment\u2010na\u00efve patients (I:EMPA first\u2010line monotherapy [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20099]; II:G\u2010CSF monotherapy [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20097]; III:EMPA plus G\u2010CSF [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916]; and IV: neither EMPA nor GCSF [\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200910]). Pediatric (P) patients were evaluated separately. In pediatric patients receiving EMPA as first\u2010line monotherapy (P\u2010I) and those with EMPA plus G\u2010CSF (P\u2010III), the frequency of infections, hospital admissions, and IBD was significantly lower than in patients receiving GCSF\u2010monotherapy (P\u2010II) or no treatment (P\u2010IV). Additionally, significantly improved weight gain was observed in P\u2010I. While clinical improvement related to correction of neutrophil dysfunction was seen with EMPA first\u2010line monotherapy (P\u2010I), significant improvement in absolute neutrophil count (ANC) and hemoglobin levels was only seen in P\u2010III with additional G\u2010CSF treatment. In three cases, EMPA was safely paused and subsequently resumed, for example, during pregnancy or liver transplantation. First\u2010line EMPA monotherapy effectively corrects clinical symptoms of neutrophil dysfunction in GSD Ib patients, even in the absence of a statistically significant increase in ANC.\n                  <\/jats:p>","DOI":"10.1002\/jimd.70198","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T02:52:24Z","timestamp":1777863144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Shifting Towards Empagliflozin First\u2010Line Therapy in Glycogen Storage Disease Type Ib: A Nationwide Real\u2010World Study"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9574-7841","authenticated-orcid":false,"given":"Sema Kalkan","family":"U\u00e7ar","sequence":"first","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neslihan \u00d6nenli","family":"Mungan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Cukurova University Faculty of Medicine  Adana T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fclden Fatma","family":"G\u00f6k\u00e7ay","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7256-0750","authenticated-orcid":false,"given":"Ay\u015fe \u00c7i\u011fdem Aktu\u011flu","family":"Zeybek","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebile","family":"K\u0131lavuz","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism and Nutrition, Department of Pediatrics Marmara University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seda","family":"G\u00fcne\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics, Faculty of Medicine Harran University  \u015eanl\u0131urfa T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Karda\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism and Nutrition, Department of Pediatrics Erciyes University Faculty of Medicine  Kayseri T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6481-3172","authenticated-orcid":false,"given":"Pelin Teke","family":"K\u0131sa","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism and Nutrition, Department of Pediatrics Dokuz Eylul University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u0131smet","family":"\u00c7\u0131k\u0131","sequence":"additional","affiliation":[{"name":"Pediatric Metabolism Unit, Department of Pediatrics, Faculty of Medicine Hacettepe University  Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aynur K\u00fc\u00e7\u00fck\u00e7ongar","family":"Yava\u015f","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases Ankara Bilkent City Hospital  Ankara T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9563-0296","authenticated-orcid":false,"given":"Ay\u00e7a Burcu","family":"Kahraman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism Konya City Hospital, University of Health Sciences  Konya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-9807","authenticated-orcid":false,"given":"Merve Yolda\u015f","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolism Adana City Training and Research Hospital  Adana T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru","family":"Canda","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deniz","family":"Kor","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Cukurova University Faculty of Medicine  Adana T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0662-7344","authenticated-orcid":false,"given":"Meryem","family":"Karaca","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7159-4008","authenticated-orcid":false,"given":"Tanyel","family":"Z\u00fcbario\u011flu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emine","family":"Gen\u00e7","sequence":"additional","affiliation":[{"name":"Division of Pediatric Metabolism and Nutrition, Department of Pediatrics Marmara University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2564-7420","authenticated-orcid":false,"given":"Havva","family":"Yaz\u0131c\u0131","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0529-2404","authenticated-orcid":false,"given":"Fatma Derya","family":"Bulut","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Cukurova University Faculty of Medicine  Adana T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015eebnem","family":"K\u0131l\u0131\u00e7","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u0131m","family":"Aghak\u0131sh\u0131l\u0131","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-9290","authenticated-orcid":false,"given":"Fehime Erdem","family":"Karap\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Metabolism and Nutrition Van Research and State Hospital  Van T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2936-058X","authenticated-orcid":false,"given":"Ezgi","family":"Burga\u00e7","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics Cukurova University Faculty of Medicine  Adana T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5170-5594","authenticated-orcid":false,"given":"Ertu\u011frul","family":"K\u0131yk\u0131m","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nutrition and Metabolism, Department of Pediatrics \u0130stanbul University Cerrahpa\u015fa Faculty of Medicine  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-6548","authenticated-orcid":false,"given":"Alperen","family":"Elek","sequence":"additional","affiliation":[{"name":"Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nihal","family":"Karda\u015f","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Department of Pediatrics Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekrem","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences Medical Point Hospital, Hasan Kalyoncu University  Gaziantep T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuba Hilkay","family":"Karap\u0131nar","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology Dr. Behcet Uz Pediatric Diseases and Surgery Training and Research Hospital  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meryem","family":"Albayrak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology Oncology K\u0131r\u0131kkale University Faculty of Medicine  K\u0131r\u0131kkale T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Canan","family":"Albayrak","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Ondokuz Mayis University  Samsun T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015feg\u00fcl","family":"\u00dcn\u00fcvar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine Istanbul University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia B.","family":"Wortmann","sequence":"additional","affiliation":[{"name":"University Children's Hospital Paracelsus Medical University  Salzburg Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1637-4678","authenticated-orcid":false,"given":"Deniz Y\u0131lmaz","family":"Karap\u0131nar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology, Department of Pediatrics Ege University Faculty of Medicine  \u0130zmir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,3]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"1993","volume-title":"GeneReviews\u00ae [Internet]","author":"Bali D. S.","year":"2021"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.13666"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.128"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010002\u20101010\u20100"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816143116"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics13101803"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019004465"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010023\u201004884\u20108"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2022.04.001"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108486"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023012403"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem\u20102024\u20100556"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010024\u201003137\u20106"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201059320\u2010z"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291\u2010025\u201000795\u20105"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21649"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12509"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/PG9.0000000000000356"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.1071464"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12278"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1365700"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12304"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2024.108144"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2025.109057"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1145111"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2024.156077"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1067\/mpd.2000.105232"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12825"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2023.100977"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmd2.12295"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1116864"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.70040"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70198","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jimd.70198","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jimd.70198","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T08:34:48Z","timestamp":1784622888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jimd.70198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":32,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jimd.70198"],"URL":"https:\/\/doi.org\/10.1002\/jimd.70198","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-12-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70198"}}