Pubertal metformin reduced adiposity in girls with low birth weight, precocious pubarche

Five years of treatment with pubertal metformin therapy reduced total, hepatic and visceral adiposity beyond puberty and improved the adipokine profile of low birth weight girls with precocious pubarche.

The small study included 38 girls (mean age, 7.9 years) born at low birth weight (mean, 2.4 kg after 38.6 weeks gestation) who had precocious pubarche. Researchers randomly assigned girls to receive metformin across puberty — 425 mg per day for two years then increased to 850 mg per day for two years — or to no treatment. Then, all girls were monitored for one year without intervention.

The researchers published data for the latter year, changes between zero and five years and changes between four and five years.

“Metformin therapy in low birth weight girls with precocious puberty, when started at about age 8 years, and given for four years across puberty, has broadly normalizing effects, most of which seem to persist for at least one year beyond stopping metformin intake,” they wrote.

During the posttreatment year, the benefits of metformin were mostly maintained. After five years, metformin therapy was associated with more lean mass; less total, hepatic and visceral fat; lowering circulating androgen and leptin levels; and elevated high-molecular-weight adiponectin and undercarboxylated osteocalcin levels.

Pubertal therapy was also associated with a more normal age at menarche — mean age of 12.4 years in 17 of 19 metformin-treated girls vs. mean age of 11.4 years in all untreated girls (P<.0001).

The metformin vs. untreated subgroups “followed diverging tracks during the four years of active treatment” but followed mostly parallel tracks across year five. In year five, height gain, lean mass, leptinemia and circulating dehydroepiandrosterone sulfate started to diverge. Insulin-like growth factor I levels in metformin-treated girls were lower than untreated girls during four years of active treatment but converged toward control levels in year five.

“At present, each of the seven randomized, placebo-controlled, metformin trials in nondiabetic children indicates that the effects shown in the present study — particularly those related to body weight, abdominal fat, visceral fat, leptinemia and/or insulin sensitivity — are attributable to the pharmacologic actions of metformin, rather than to a long-term placebo effect,” the researchers wrote.

Ibanez L. J Pediatr. 2010;156:98-102.