{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T04:43:07Z","timestamp":1787719387045,"version":"build-2784847793"},"reference-count":42,"publisher":"American Academy of Pediatrics (AAP)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVES:<\/jats:title>\n                  <jats:p>Metformin has shown its effectiveness in treating obesity in adults. However, little research has been conducted in children, with a lack of attention on pubertal status. The objectives were to determine whether oral metformin treatment reduces BMI z score, cardiovascular risk, and inflammation biomarkers in children who are obese depending on pubertal stage and sex.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>This was a randomized, prospective, double-blind, placebo-controlled, multicenter trial, stratified according to pubertal stage and sex, conducted at 4 Spanish clinical hospitals. Eighty prepubertal and 80 pubertal nondiabetic children who were obese aged 7 to 14 years with a BMI &amp;gt;95th percentiles were recruited. The intervention included 1 g\/d of metformin versus placebo for 6 months. The primary outcome was a reduction in BMI z score. Secondary outcomes comprised insulin resistance, cardiovascular risk, and inflammation biomarkers.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>A total of 140 children completed the study (72 boys). Metformin decreased the BMI z score versus placebo in the prepubertal group (\u22120.8 and \u22120.6, respectively; difference, 0.2; P = .04). Significant increments were observed in prepubertal children treated with metformin versus placebo recipients in the quantitative insulin sensitivity check index (0.010 and \u22120.007; difference, 0.017; P = .01) and the adiponectin\u2013leptin ratio (0.96 and 0.15; difference, 0.81; P = .01) and declines in interferon-\u03b3 (\u22125.6 and 0; difference, 5.6; P = .02) and total plasminogen activator inhibitor-1 (\u22121.7 and 2.4; difference, 4.1; P = .04). No serious adverse effects were reported.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>Metformin decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters in prepubertal children but not in pubertal children. Hence, the differential response according to puberty might be related to the dose of metformin per kilogram of weight. Further investigations are necessary.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2016-4285","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T09:10:33Z","timestamp":1497258633000},"source":"Crossref","is-referenced-by-count":61,"title":["Metformin for Obesity in Prepubertal and Pubertal Children: A Randomized Controlled Trial"],"prefix":"10.1542","volume":"140","author":[{"given":"Bel\u00e9n","family":"Pastor-Villaescusa","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. Spain;"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dolores","family":"Ca\u00f1ete","sequence":"additional","affiliation":[{"name":"PAIDI CTS-329, Maimonides Institute of Biomedical Research of C\u00f3rdoba (IMIBIC), C\u00f3rdoba, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Caballero-Villarraso","sequence":"additional","affiliation":[{"name":"Clinical Analysis Services, IMIBIC\/Reina Sof\u00eda Hospital, C\u00f3rdoba University, C\u00f3rdoba, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ra\u00fal","family":"Hoyos","sequence":"additional","affiliation":[{"name":"Pediatric Department and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Latorre","sequence":"additional","affiliation":[{"name":"Health Sciences Institute in Aragon, Zaragoza, Spain;"},{"name":"Pediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo","family":"V\u00e1zquez-Cobela","sequence":"additional","affiliation":[{"name":"Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Plaza-D\u00edaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. Spain;"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Pediatric Gastroenterology and Nutrition Unit, Virgen de las Nieves University Hospital, Andalusian Health Service, Granada, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Bueno","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"},{"name":"Pediatric Department, Lozano Blesa University Clinical Hospital, University of Zaragoza, Zaragoza, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosaura","family":"Leis","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"},{"name":"Unit of Investigation in Nutrition, Growth and Human Development of Galicia, Pediatric Department, Clinic University Hospital of Santiago, University of Santiago de Compostela, Santiago de Compostela, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1ngel","family":"Gil","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. Spain;"},{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Granada, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram\u00f3n","family":"Ca\u00f1ete","sequence":"additional","affiliation":[{"name":"CIBER Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN), Madrid, Spain;"},{"name":"Unit of Pediatric Endocrinology, Reina Sofia University Hospital, C\u00f3rdoba, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concepci\u00f3n M.","family":"Aguilera","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. 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