Department of Biochemistry and Molecular Biology II, Institute of Nutrition and Food Technology, Center for Biomedical Research, University of Granada, Granada. Spain.
CIBER Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Madrid, Spain.
Pediatrics. 2017 Jul;140(1). doi: 10.1542/peds.2016-4285. Epub 2017 Jun 12.
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 score, cardiovascular risk, and inflammation biomarkers in children who are obese depending on pubertal stage and sex.
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 >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 score. Secondary outcomes comprised insulin resistance, cardiovascular risk, and inflammation biomarkers.
A total of 140 children completed the study (72 boys). Metformin decreased the BMI score versus placebo in the prepubertal group (-0.8 and -0.6, respectively; difference, 0.2; = .04). Significant increments were observed in prepubertal children treated with metformin versus placebo recipients in the quantitative insulin sensitivity check index (0.010 and -0.007; difference, 0.017; = .01) and the adiponectin-leptin ratio (0.96 and 0.15; difference, 0.81; = .01) and declines in interferon-γ (-5.6 and 0; difference, 5.6; = .02) and total plasminogen activator inhibitor-1 (-1.7 and 2.4; difference, 4.1; = .04). No serious adverse effects were reported.
“Metformin decreased the BMI z score and improved inflammatory and cardiovascular-related obesity parameters only in prepubertal children, but a differential effect of metformin was not observed in prepubertal compared to pubertal children. Nevertheless, the doses per kilogram of weight administrated may have had an impact on the metformin effect. Further investigations are necessary.”
二甲双胍已被证明可有效治疗成年人肥胖。然而，针对儿童肥胖的研究较少，且对青春期状态关注不足。本研究旨在确定口服二甲双胍治疗是否可降低肥胖儿童的 BMI 评分、心血管风险和炎症生物标志物，具体取决于青春期阶段和性别。
这是一项在西班牙 4 家临床医院进行的、随机、前瞻性、双盲、安慰剂对照、多中心试验，按青春期阶段和性别分层。共纳入 80 名肥胖且未进入青春期的 7 至 14 岁儿童和 80 名肥胖且进入青春期的非糖尿病儿童，其 BMI 超过第 95 百分位数。干预措施包括二甲双胍 1 g/d 或安慰剂治疗 6 个月。主要结局为 BMI z 评分降低。次要结局包括胰岛素抵抗、心血管风险和炎症生物标志物。
共有 140 名儿童完成了研究（72 名男孩）。与安慰剂相比，二甲双胍可降低未进入青春期组儿童的 BMI z 评分（分别为-0.8 和-0.6，差值为 0.2；P =.04）。与安慰剂组相比，接受二甲双胍治疗的未进入青春期儿童的定量胰岛素敏感性检查指数（0.010 与-0.007，差值为 0.017；P =.01）和脂联素-瘦素比值（0.96 与 0.15，差值为 0.81；P =.01）显著升高，干扰素-γ（-5.6 与 0，差值为 5.6；P =.02）和总纤溶酶原激活物抑制剂-1（-1.7 与 2.4，差值为 4.1；P =.04）水平降低。未报告严重不良事件。
“二甲双胍可降低 BMI z 评分，并改善炎症和心血管相关肥胖参数，仅在未进入青春期的儿童中有效，但在未进入青春期和进入青春期的儿童中，二甲双胍的作用无差异。然而，每公斤体重的给药剂量可能对二甲双胍的疗效有影响。需要进一步研究。”
