Pubertal Metformin Therapy to Reduce Total, Visceral, and Hepatic Adiposity

Objective

Puberty is part of a critical window in which adiposity and its correlates can be fine-tuned toward reproduction, which implies that puberty provides an opportunity to reprogram a misprogramming that occurred in early life. We tested this hypothesis in low-birthweight (LBW) girls with precocious pubarche (PP), who are at risk for hyperinsulinemic body adiposity during and beyond puberty.

Study design

LBW girls with PP (n = 38; mean age 8 years) were randomized to remain untreated or to receive metformin across puberty (425 mg/d for 2 years, then 850 mg/d for 2 years); subsequently, all girls were monitored for 1 year without intervention. Here we report on the latter year.

Results

The benefits of metformin were mostly maintained during the posttreatment year so that, after 5 years, metformin therapy was associated with more lean mass; with less total, visceral, and hepatic fat; with lower circulating levels of androgens and leptin; and with elevated levels of high-molecular-weight adiponectin and undercarboxylated osteocalcin.

Conclusion

In LBW girls with PP, pubertal metformin therapy was followed by a favorable adipokine profile and by a reduction of total, visceral, and hepatic adiposity beyond puberty.

AI, Average intensity, DHEAS, Dehydroepiandrosterone sulfate, HMW, High-molecular-weight, IGF-1, Insulin-like growth factor 1, IHLC, Intrahepatic lipid content, LBW, Low-birthweight, MRI, Magnetic resonance imaging, PP, Precocious pubarche, SHBG, Sex hormone binding globulin