Abstract
BackgroundMetformin treatment (1000–2000 mg/day) over 6 months in pubertal children and/or adolescents with obesity and hyperinsulinism is associated with a reduction in body mass index (BMI) and the insulin resistance index (HOMA-IR). We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrine-metabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity.MethodsA pilot double-blind, placebo-controlled trial was conducted on 18 pre-puberal and early pubertal (Tanner stage I-II) children with obesity and risk markers for metabolic syndrome. Patients were randomly assigned (1:1) to receive metformin (850 mg/day) or placebo for 24 months. Clinical, biochemical (insulin, lipids, leptin, and high-sensitivity C-reactive protein [hsCRP]), and imaging (body composition [dual-energy X-ray absorptiometry and magnetic resonance imaging]) parameters as well as cIMT (ultrasonography) were assessed at baseline and at 6, 12, and 24 months.ResultsThe 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), BMI-SDS, leptin, leptin–to–high-molecular-weight (HMW) adiponectin ratio, hsCRP, cIMT, fat mass, and liver fat in metformin-treated children compared with placebo. The effect of metformin on the reduction of BMI-SDS, leptin, leptin-to-HMW adiponectin ratio, hsCRP, and liver fat seemed to be maintained after completing the 24 months of treatment. No changes in insulin sensitivity (HOMA-IR) or adverse effects were detected.ConclusionIn this pilot study, metformin treatment in pre-puberal and early pubertal children with obesity seemed to improve body composition and inflammation markers. Our data encourage the development of future fully powered trials using 850 mg/day metformin in young children, highlighting its excellent tolerance and potential long-term benefits.
Highlights
Obesity is an important public health problem, owing to the exponential increase in its prevalence in recent years [1]; the prevalence of pediatric obesity has tripled in one decade in Spain [2]
The 12-month treatment tend to cause a reduction in weight standard deviation scores (SDS), body mass index (BMI)-SDS, leptin, leptin–to–high-molecular-weight (HMW) adiponectin ratio, high-sensitivity C-reactive protein (hsCRP), carotid intima-media thickness (cIMT), fat mass, and liver fat in metformin-treated children compared with placebo
It has been successfully used to reduce weight gain, hyperinsulinemia, and dyslipidemia in adults, and in patients with prediabetes, to prevent the progression from glucose intolerance to type 2 diabetes [8, 9]. These results have prompted the use of metformin in adolescents in the early phases of development of diabetes and metabolic syndrome, mainly in those patients with obesity and hyperinsulinemia, in order to reduce the risk for metabolic and cardiovascular diseases [10]
Summary
Obesity is an important public health problem, owing to the exponential increase in its prevalence in recent years [1]; the prevalence of pediatric obesity has tripled in one decade in Spain [2]. The mainstay of prevention and treatment of obesity in children is based on lifestyle modification including diet and physical activity; long-term compliance to these remains very poor While some of these programs have shown to be effective in improving anthropometric parameters, there is conflicting evidence about their effectiveness in improving the body composition and reversing the insulin resistance and metabolic derangements [4, 5]. It has been successfully used to reduce weight gain, hyperinsulinemia, and dyslipidemia in adults, and in patients with prediabetes, to prevent the progression from glucose intolerance to type 2 diabetes [8, 9] These results have prompted the use of metformin in adolescents in the early phases of development of diabetes and metabolic syndrome, mainly in those patients with obesity and hyperinsulinemia, in order to reduce the risk for metabolic and cardiovascular diseases [10]. We aimed to ascertain if long-term treatment (24 months) with lower doses of metformin (850 mg/day) normalizes the endocrinemetabolic abnormalities, improves body composition, and reduces the carotid intima-media thickness (cIMT) in pre-puberal and early pubertal children with obesity
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