Metformin treatment to reduce central adiposity after prenatal growth restraint: a placebo-controlled pilot study in prepubertal children

BackgroundChildren born small-for-gestational-age (SGA) who experience rapid postnatal catch-up in weight are at risk for central adiposity and hyperinsulinemia. ObjectivesTo study the effects of prepubertal metformin intervention over 24 months on the body composition and endocrine-metabolic profile of catch-up SGA children. MethodsDouble-blind, placebo-controlled, pilot study including 23 post-catch-up non-obese prepubertal SGA children [age, 7.7 yr; body mass index standard deviation score (BMI SDS) >50th and <97th centile for age] with increased visceral fat [by magnetic resonance imaging (MRI) and insulin-like growth factor-I (IGF-I) both p > 75th for age]. Patients were randomized to receive either placebo or metformin (425 mg/d) for 24 months. Clinical, biochemical [IGF-I, glucose, insulin, lipids, androgens, sex-hormone-binding globulin (SHBG) and high-molecular-weight (HMW)-adiponectin] and imaging [body composition (absorptiometry and MRI; carotid intima-media thickness (ultrasonography)] variables were assessed at baseline, and at 6, 12, and 24 months. ResultsAfter 24 months, metformin-treated children were leaner, had higher SHBG levels, and less total and abdominal fat than placebo-treated children (all p 0.05). Longitudinal analyses showed that metformin had a significant effect on anthropometric (weight, BMI, and waist) and biochemical variables [glucose, homeostasis model assessment-insulin resistance (HOMA-IR), and triglycerides] (all p 0.05); and in total and abdominal fat (p = 0.01 and p = 0.02). ConclusionsPrepubertal intervention with metformin reduces central adiposity and improves insulin sensitivity in non-obese catch-up SGA children.