{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T10:04:03Z","timestamp":1779789843689,"version":"3.53.1"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":16,"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":["Endocrino Diabet &amp; Metabol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n The use of metformin among children and adolescents has risen in the past decade; however, its effect on vitamin B12 has been unclear. To address this gap, we conducted this first systematic review and single\u2010arm meta\u2010analysis.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To investigate the effect of metformin on vitamin B12 levels.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n PubMed, Scopus and Web of Science were systematically searched until April 2025. The primary outcomes were the effect of metformin on vitamin B12 levels after 6 and 12\u2009months of duration, and vitamin B12 deficiency after at least 12\u2009months of usage. We conducted the risk\u2010of\u2010bias assessment using the NOS and Cochrane ROB2 tool. The mean difference (MD) and standard error (SE) were calculated and used for analysis. We assessed the heterogeneity of the studies using the chi\u2010squared test and measured it with the\n I<\/jats:italic>\n 2<\/jats:sup>\n statistic. A fixed effects model was applied to calculate the pooled MD in the absence of significant heterogeneity. The registration number in PROSPERO 2025 is CRD420251045023.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of five articles were included in this systematic review and meta\u2010analysis. The pooled rate of vitamin B12 deficiency in RCT studies after at least 12\u2009months of use was 1.4% [95% CI: \u22120.012, 0.040] with mild heterogeneity (\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200930.87%,\n p<\/jats:italic>\n \u2009=\u20090.235). While in observational studies the pooled rate was 18.7% [95% CI: \u22120.212, 0.586] with substantial heterogeneity (\n I<\/jats:italic>\n 2<\/jats:sup>\n \u2009=\u200987.93%,\n p<\/jats:italic>\n \u2009=\u20090.004). Vitamin B12 levels decreased after 6 and 12\u2009months of using metformin; however, it was neither statistically nor clinically significant (\n p<\/jats:italic>\n \u2009>\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n More trials with larger sample sizes and longer durations of follow\u2010up are needed to better understand the risk of vitamin B12 deficiency among the paediatric population.<\/jats:p>\n \n Trial Registration:<\/jats:bold>\n PROSPERO (CRD420251045023).\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/edm2.70232","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T05:58:42Z","timestamp":1779083922000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Impact of Metformin on Vitamin\n B12<\/scp>\n Levels in Children and Adolescents: A Systematic Review and Single\u2010Arm Meta\u2010Analysis"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1977-7585","authenticated-orcid":false,"given":"Einas Abdullah","family":"Tahir","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Khartoum Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhtadi G.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Mansoura University Mansoura Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9228-2943","authenticated-orcid":false,"given":"Motasam Belah","family":"Al Swayah","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Tripoli Tripoli Libya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Mostafa","family":"Elsayed","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhan Ahmed","family":"Alnoaimi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Mohamed","family":"Hegazy","sequence":"additional","affiliation":[{"name":"Acute Medicine Medway NHS Foundation Trust Gillingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada Sayed","family":"Abdelalim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine Fayoum University Fayoum Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rehab Adel","family":"Diab","sequence":"additional","affiliation":[{"name":"Cardiology Department, Faculty of Medicine Al\u2010Azhar University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010017\u20104318\u2010z"},{"key":"e_1_2_14_3_1","volume-title":"Glucophage (Metformin Hydrochloride) Tablets [Package Insert]","author":"Food and Drug 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