The effects of metformin on insulin resistance in overweight or obese children and adolescents: A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Metformin has shown its effectiveness in reducing body mass index (BMI) in obese children and adolescents, but relevant evidence for improving insulin resistance in overweight or obese children and adolescents is inconclusive. OBJECTIVES: This study aimed to assess whether metformin could effectively and safely improve homeostasis model assessment insulin resistance index (HOMA-IR) and other related laboratory indicators including fasting glucose, fasting insulin, high-density lipoprotein cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C). METHODS: Searches were carried out in PubMed, CENTRAL, Web of Science, EMBASE, CBM, Chinese National Knowledge Infrastructure (CNKI), and WanFang from their inception until March 2018. Randomized controlled trials (RCTs) comparing metformin alone with placebo in overweight or obese children and adolescents were included. The Cochrane risk of bias tool was applied to assess the methodological quality of every study and Meta-analysis was carried out with a random effects model or a fixed effects model. Publication bias was evaluated by the Begg and Egger tests. RESULTS: A total of 11 trials with a total of 865 participants met the inclusion criteria. Participants were between 4 and 18 years old. The time span of these studies ranged from 2001 to 2017. The daily dose of metformin was from 1000 mg to 2000 mg and the duration of intervention was 8 weeks to 18 months. Compared with placebo, metformin with lifestyle intervention reduced the level of LDL-C (P = 008, MD = - 4.29, 95% confidence interval [CI]: -7.45, -1.12). However, there was no obvious differences in improving insulin resistance, fasting glucose, and HDL-C. CONCLUSION: Metformin may improve the level of LDL-C, but it has no significant effect on insulin resistance. The use of metformin may be a new approach to lipid metabolism management in overweight or obese children and adolescents. REGISTRATION NUMBER: CRD42018092059.