Metformin for Rapidly Maturing Girls with Central Adiposity: Less Liver Fat and Slower Bone Maturation

<b><i>Background/Aims:</i></b> Girls with low-birth weight (LBW) and postnatal weight catch-up tend to develop visceral and hepatic fat excess, which may be accompanied by an upregulated adrenarche with precocious pubarche (PP) and by a rapidly progressive puberty with early menarche and shorter stature. A pilot study suggested that metformin treatment for 4 years reduces central adiposity in LBW-PP girls and normalizes puberty and adult height. In this cohort, we studied the relationship between metformin treatment, bone maturation, and body composition. <b><i>Methods:</i></b> Longitudinal hand X-rays (0–4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; <i>n</i> = 17 untreated, <i>n</i> = 17 metformin-treated; age at the start of treatment 8 years) along with body composition (0–4 years, by DXA), hepatic fat, and abdominally subcutaneous and visceral fat (posttreatment, by MRI). <b><i>Results:</i></b> The tempo of bone aging was accelerated in untreated girls (≈16% faster vs. chronological aging) and normal in metformin-treated girls (≈20% slower vs. untreated girls). Metformin-treated girls gained more height per bone-age year and had less visceral and hepatic fat. The tempo of bone maturation was associated (<i>R</i> = 0.55; <i>p</i> &#x3c; 0.001) with hepatic fat. <b><i>Conclusion:</i></b> Metformin treatment in rapidly maturing girls with central adiposity normalized bone maturation. This normalization was accompanied by less central fat and was related closely to hepatic fat.