{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:01:47Z","timestamp":1788483707489,"version":"build-2803163510"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Although metformin is the first-line medicine for type 2 diabetes (T2D), its safety profile in adolescents remains poorly understood. This study seeks to investigate the adverse events linked to metformin use in adolescents diagnosed with T2D.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data from the Food and Drug Administration Adverse Event Reporting System (FAERS), spanning Q1 2004 to Q2 2024, were retrospectively analyzed in this study. Adverse reactions were standardized using the Medical Dictionary for Regulatory Activities, then significant adverse drug reaction signals were identified through disproportionality analysis employing reporting odds ratio (ROR) and information component (IC) methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 17,956,653 FAERS reports, 80,187 involved metformin, including 973 in adolescents (10\u201319 years), with 174 cases were identified with a T2D indication. Analysis at the system organ class level revealed that congenital, familial, and genetic disorders [ROR: 8.8 (4.0, 19.3); IC: 2.2 (1.1, 2.9)] and pregnancy conditions [ROR: 4.9 (2.5, 9.5); IC: 1.8 (0.8, 2.5)] showed the most significant signals. At the preferred term (PT) level, three signals were identified across all sexes and subgroups: treatment noncompliance [ROR: overall 4.14 (2.44, 7.02), male 4.27 (2.00, 9.12), and female 4.65 (2.22, 9.74); IC: overall 1.67 (0.88, 2.22), male 1.60 (0.46, 2.36), and female 1.74 (0.60, 2.50)], lactic acidosis [IC: overall 2.99 (1.91, 3.72), male 2.53 (0.76, 3.61), and female 2.76 (1.34, 3.67)], and gastrointestinal disorder [ROR: overall 13.09 (4.73, 36.23), male 54.33 (6.05, 487.96), female 5.34 (1.10, 25.84)]. Neurological disorders were observed only in males, while pregnancy-related adverse effects and renal disorders occurred exclusively in females. Additionally, the study identified potential new signals not documented in metformin labeling, including areflexia, muscle weakness, ataxia, decreased vibratory sense, rhabdomyolysis, substance use, and axillary pain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The study reveals a complex safety profile of metformin in adolescents with T2D, warranting further research to confirm risks.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0337204","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T18:21:46Z","timestamp":1763749306000},"page":"e0337204","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Safety profile of metformin in adolescents with type 2 diabetes: A pharmacovigilance analysis of the FDA Adverse Event Reporting System"],"prefix":"10.1371","volume":"20","author":[{"given":"Mengsi","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-In","family":"Joung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6473-0748","authenticated-orcid":true,"given":"Kwang Joon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"issue":"10085","key":"pone.0337204.ref001","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1016\/S0140-6736(17)31371-5","article-title":"Type 2 diabetes in adolescents: a severe phenotype posing major clinical challenges and public health burden","volume":"389","author":"R Viner","year":"2017","journal-title":"Lancet"},{"issue":"6","key":"pone.0337204.ref002","doi-asserted-by":"crossref","first-page":"161","DOI":"10.15585\/mmwr.mm6906a3","article-title":"Trends in incidence of type 1 and type 2 diabetes among youths - selected counties and indian reservations, United States, 2002-2015","volume":"69","author":"J Divers","year":"2020","journal-title":"MMWR Morb Mortal Wkly Rep"},{"issue":"15","key":"pone.0337204.ref003","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1056\/NEJMoa1610187","article-title":"Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012","volume":"376","author":"EJ Mayer-Davis","year":"2017","journal-title":"N Engl J Med"},{"issue":"12","key":"pone.0337204.ref004","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.2337\/dc12-0669","article-title":"Projections of type 1 and type 2 diabetes burden in the U.S. population aged <20 years through 2050: dynamic modeling of incidence, mortality, and population growth","volume":"35","author":"G Imperatore","year":"2012","journal-title":"Diabetes Care"},{"issue":"7","key":"pone.0337204.ref005","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1007\/s11892-016-0751-5","article-title":"Insulin resistance of puberty","volume":"16","author":"MM Kelsey","year":"2016","journal-title":"Curr Diab Rep"},{"issue":"9","key":"pone.0337204.ref006","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.2337\/dc21-0027","article-title":"Baseline predictors of glycemic worsening in youth and adults with impaired glucose tolerance or recently diagnosed type 2 diabetes in the Restoring Insulin Secretion (RISE) Study","volume":"44","author":"S Sam","year":"2021","journal-title":"Diabetes Care"},{"issue":"1","key":"pone.0337204.ref007","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-8587(17)30186-9","article-title":"Type 2 diabetes in adolescents and young adults","volume":"6","author":"N Lascar","year":"2018","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"5","key":"pone.0337204.ref008","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1056\/NEJMoa2100165","article-title":"Long-term complications in youth-onset type 2 diabetes","volume":"385","author":"TODAY Study Group","year":"2021","journal-title":"N Engl J Med"},{"key":"pone.0337204.ref009","article-title":"14. 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