Metformin for Obese, Nondiabetic Children? No Meaningful Weight Loss

Marlene Busko

December 17, 2013

Among obese children without type 2 diabetes, adding metformin to lifestyle counseling did not lead to a "dramatic" or "clinically important" short-term weight loss, in a review of 14 studies, lead author Marian S. McDonagh, PharmD, from Oregon Health & Science University, in Portland, told Medscape Medical News.Some individual children might "benefit from a small decrease [in weight] to get the ball rolling, but otherwise this is not going to be the 'silver bullet,' " she added.

The largest improvement in body mass index (BMI) was in the pooled 6-month studies, where metformin resulted in a drop in BMI that was 3.6% greater than that seen with lifestyle interventions alone. However, this was "less than the 5% to 10% goals often cited as a marker for meaningful weight loss," the authors write.

"This is not going to be your go-to treatment for these obese children," McDonagh summarized. "It will be the rare child that you'll say 'Okay, this person just might benefit from this little jumpstart for 6 months' — but really, these are not great results."

The review was published online December 16 in JAMA Pediatrics.

Need for New Approaches for Childhood Obesity

In 2008, an estimated 16.9% of children in the United States were obese, and these children are more likely to grow into obese adults and have diabetes, hypertension, and abnormal serum lipids, the authors write. Many children find it difficult to lose weight with diet and exercise. Orlistat ( Xenical, Genentech) has been approved by the US Food and Drug Administration since 2003 for obesity in adolescents aged 12 to 16 years. Bariatric surgery is generally restricted to adults.

There is a need to identify new approaches for childhood obesity, the authors write. There has been a lot of interest in metformin, which is linked to weight loss in adults and which has long been approved to treat diabetes in children over age 10, Dr. McDonagh explained. A 2008 review looked at using metformin off-label for weight loss in children.

The researchers conducted an updated review to evaluate the effectiveness and safety of metformin for treating overweight or obese children or adolescents who did not have diabetes.

They identified 14 clinical trials published from 1996 to 2012 that compared lifestyle interventions — mostly not very intensive diet and exercise advice — vs lifestyle interventions plus metformin.

The trials were small, ranging from 24 to 173 participants. They enrolled a total of 946 children and adolescents aged 8 to 18 years (mean age, 10 to 16 years), who had a BMI of 26 to 41 (mean, 33). Most studies were 6 months to 12 months (8 studies), whereas 4 were less than 6 months, and 2 were at least 1 year. Metformin doses ranged from 1000 to 2000 mg a day.

Modest Overall Benefit; Subgroups Need Further Study

The largest benefit from metformin was seen in the pooled estimate of seven 6-month trials. The patients who received metformin lost 3.77 kg more and had a 1.4 greater drop in BMI compared with patients who received lifestyle intervention alone.

In the 2 studies with data at 1 year (250 patients), BMI changes were not clearly different with metformin vs lifestyle alone.

Compared with patients in the control group, more patients receiving metformin reported gastrointestinal events (26% vs 13%). There were no serious adverse events, and there was no difference in discontinuation for adverse events.

"Subgroup analyses suggest that there may be children who benefit more — for example, those with BMI greater than 35, those age 12 years or younger, and those who have not failed lifestyle interventions previously," Dr. McDonagh and colleagues write. The review also suggests that effects were smaller in studies with more girls or adolescents and in Hispanic patients or those with acanthosis nigricans.

A larger trial is needed to fully examine potential subgroups that might benefit from metformin and account for major potential confounding factors such as puberty, they add. "In the context of other options for treating childhood obesity, metformin has not been shown to be clinically superior," they conclude.

JAMA Pediatr. Published online December 16, 2013. Abstract

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