Context and Objective: A low birthweight (LBW) tends to be followed by overweight, due to an excess of fat, including visceral fat. LBW girls with precocious pubarche (PP; pubic hair <8 yr) are at high risk for developing an adipose state of hyperinsulinemic androgen excess that leads towards early menarche. We explored the effects of insulin sensitization with metformin in LBW-PP girls.

Setting, Design, Patients, Intervention: Prepubertal LBW girls with PP [mean BW 2.4 Kg; age 7.9 yr; body mass index (BMI) 18.4 Kg/m²]; girls were randomly assigned to remain untreated (n=19) or to receive metformin for 4 yr (n=19; 425 mg/d for 2 yr, then 850 mg/d for 2 yr).

Main outcomes: at start and after 4 yr: height, weight; fasting insulin, glucose, IGF-I, testosterone, lipids, leptin, high-molecular weight (HMW)-adiponectin; body composition by absorptiometry; abdominal fat partitioning (only 4 yr) by magnetic resonance imaging; menarcheal status.

Results: Metformin-treated girls gained on average 5.5 Kg (or 50%) less fat, were after 4 yr less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, while their gains in height, lean mass and bone mineral density were similar. After 4 yr, untreated girls had more visceral fat, a higher ratio of visceral-to-subcutaneous fat, and a higher leptin-to-HMW adiponectin ratio (all 50% higher) than metformin-treated girls.

Conclusion: Long-term metformin treatment appears to reduce total and visceral fat in LBW-PP girls, and to delay menarche without attenuating linear growth, thereby opening the perspective that adult height may be increased.