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

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.

Longitudinal hand X-rays (0-4 years, analyzed by BoneXpert) were available from 34 LBW-PP girls (89% of the original cohort; n = 17 untreated, n = 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).

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 (R = 0.55; p < 0.001) with hepatic fat.

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.