title: Metformin effectiveness and safety in the management of overweight/obese nondiabetic children and adolescents: metabolic benefits of the continuous exposure to metformin at 12 and 24 months.
abstract: BACKGROUND
  Childhood obesity prevalence is rising and new therapeutical approaches are needed. Metformin is likely beneficial in obese and/or insulin-resistant children/adolescents, but its role in this setting is still unclear. We aimed to evaluate the effectiveness, in terms of weight loss and insulin resistance, and safety of metformin in nondiabetic overweight/obese children and adolescents.
  
  
  METHODS
  We retrospectively reviewed clinical records of 78 nondiabetic obese/overweight [body mass index (BMI)≥85th/95th percentile for age and sex] children and adolescents. Anthropometric and metabolic outcomes of 39 patients treated with metformin (mean daily dose: 1.3±0.5 g) were analyzed and compared to lifestyle intervention alone at different follow-up times (12 and 24 months).
  
  
  RESULTS
  The mean age of the 78 patients was 13.3 years, 41 were females and mean BMI and BMI-SDS were 32.8 kg/m2 and 3.1, respectively. There was a decrease in mean BMI-SDS within each treatment group in all periods, except at 24 months for lifestyle intervention. However, the change in BMI-SDS was not significantly superior in the metformin group when compared to lifestyle intervention. Metformin had greater effectiveness over lifestyle intervention alone in reducing fasting insulin levels and homeostasis model assessment for insulin-resistance index (HOMA-IR) at both 12 and 24 months. Five patients had gastrointestinal adverse effects (12.8%), four requiring dose reduction, but metformin could be resumed in all.
  
  
  CONCLUSIONS
  Metformin for nondiabetic obese/overweight children and adolescents resulted in a noteworthy insulin resistance improvement, without significant BMI advantage when compared to lifestyle intervention. Metformin metabolic and anthropometric effects appear to be beneficial up to 24 months, without relevant adverse effects, highlighting its potential long-term benefits.
authors.affiliation: .
authors.forename: Pedro
authors.initials: P
authors.lastname: Marques
authors.affiliation: .
authors.forename: Catarina
authors.initials: C
authors.lastname: Limbert
authors.affiliation: .
authors.forename: Laura
authors.initials: L
authors.lastname: Oliveira
authors.affiliation: .
authors.forename: Maria Inês
authors.initials: MI
authors.lastname: Santos
authors.affiliation: .
authors.forename: Lurdes
authors.initials: L
authors.lastname: Lopes
keywords: adolescents; children; insulin resistance; metformin; obesity