Another tool for adolescent obesity — this is a study geared towards 13-18 year olds who were in the 95th percentile for their BMI.

From Medscape:

Metformin Extended Release May Be Helpful for Adolescent Obesity

Laurie Barclay, MD

February 2, 2010 — Metformin hydrochloride extended release (XR) with lifestyle intervention may be helpful for the treatment of adolescent obesity, according to the results of a multicenter, randomized controlled trial reported in the February issue of the Archives of Pediatrics & Adolescent Medicine.

“Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported,” write Darrell M. Wilson, MD, from Lucile Salter Packard Children’s Hospital, Stanford University School of Medicine in Stanford, California, and colleagues from the Glaser Pediatric Research Network Obesity Study Group. “Therefore, we conducted a 48-week randomized, double-blind, placebo-controlled trial of…XR metformin therapy in nondiabetic obese adolescents, followed by a 48-week monitoring period after completion of treatment.”

The goal of the study was to test the hypothesis that 48 weeks of daily metformin XR treatment would reduce body mass index (BMI) in obese adolescents vs placebo.

From October 2003 to August 2007 at the 6 centers of the Glaser Pediatric Research Network, 78 obese adolescents following a lifestyle intervention program underwent a 1-month run-in period and were then randomly assigned 1:1 to receive 48 weeks of treatment with metformin hydrochloride XR, 2000 mg once daily or an identical placebo. At baseline, BMI was at least in the 95th percentile, and age range was 13 to 18 years. The main study endpoint was change in BMI, after adjustment for site, sex, race, ethnicity, and age, and group assignment.

Mean adjusted BMI increased by 0.2 ± 0.5 in the placebo group and decreased by 0.9 ± 0.5 in the metformin XR group (P = .03) after 48 weeks of treatment, and this difference persisted for 12 to 24 weeks after cessation of treatment. There were no significant effects of metformin on body composition, abdominal fat, or insulin indices.

“Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program,” the study authors write.

Limitations of this study include study not specifically powered to evaluate the effect of metformin on insulin and lipid indices.

“Metformin was safe and tolerated in this population,” the study authors conclude. “These results indicate that metformin may have an important role in the treatment of adolescent obesity. Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population.”

Bristol-Myers Squibb provided active drug (GlucophageXR) and placebos. The Glaser Pediatric Research Network is funded by the Elizabeth Glaser Pediatric Research Foundation, a program of the Elizabeth Glaser Pediatric AIDS Foundation. The study was supported by the Elizabeth Glaser Pediatric Research Foundation and the National Institutes of Health–supported Clinical Research Centers.

Arch Pediatr Adolesc Med. 2010;164:116-123.

Andrea’s note:  While there are some good figures that show positive outcomes for metformin treating obesity in non-diabetic children, the study was short-term, not as effective as behavior-modification, and was moderately effective as compared to other drugs on the market to treat obesity.  Additionally, the study was more geared towards minorities that are impacted with metabolic disorders — so yes, much much more study is needed… but I think it’s worth noting that this study was done and positive outcomes were found.

From Medscape:

Metformin for Obesity in Children and Adolescents: A Systematic Review

Min Hae Park, MSC; Sanjay Kinra, MD, PHD; Kirsten J. Ward, PHD; Billy White, MBBS; Russell M. Viner, MBBS, PHD

Posted: 12/14/2009; Diabetes Care. 2009;32(9):1743-1745. © 2009

Abstract

Objective—To summarize the efficacy of metformin in reducing BMI and cardiometabolic risk in obese children and adolescents without diabetes.
Research design and methods—We performed a systematic review and meta-analysis of randomized controlled trials (RCTs). Double-blind RCTs of ≥6 months duration in obese subjects age ≤19 years without diabetes were included. Our primary outcomes of interest include changes in BMI and measures of insulin sensitivity.
Results—Five trials met inclusion criteria (n = 320 individuals). Compared with placebo, metformin reduced BMI by 1.42 kg/m2 (95% CI 0.83–2.02) and homeostasis model assessment insulin of resistance (HOMA-IR) score by 2.01 (95% CI 0.75–3.26).
ConclusionsMetformin appears to be moderately efficacious in reducing BMI and insulin resistance in hyperinsulinemic obese children and adolescents in the short term. Larger, longer-term studies in different populations are needed to establish its role in the treatment of overweight children.

Introduction

Metformin has been shown to reduce weight gain, hyperinsulinemia, and hyperglycemia in adults with type 2 diabetes[1,2] and to reduce progression from impaired glucose tolerance to diabetes in those without diabetes.[3] These benefits have led to an increase in the use of metformin in obese children with hyperinsulinemia. However, obesity is not a licensed indication for metformin in the U.K. or the U.S., and its use has proceeded faster than the evidence of its benefits. We undertook a systematic review of randomized controlled trials (RCTs) investigating the efficacy of metformin for reducing BMI and cardiometabolic risk in obese children without diabetes.

Research Design and Methods

We searched Ovid MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, the metaRegister of Controlled Trials, and key journals published before December 2008 (online appendix Tables 1 and 2 available at http://care.diabetesjournals.org/cgi/content/full/dc09-0258/DC1). We included double-blind RCTs of ≥6 months duration with obese subjects age ≤19 years without diabetes and without secondary or syndromic causes of obesity. Primary outcomes of interest were BMI (weight in kilograms divided by the square of height in meters) and measures of insulin sensitivity. Secondary outcomes included fat mass, blood pressure, fasting lipids, and adverse effects.

Where three or more studies reported a common outcome, treatment effect was explored in a meta-analysis (Stata Statistical Software 10.1; StataCorp, College Station, TX), pooling data from the end of the follow-up period for trial completers. A random-effects model was selected. Sensitivity analyses were performed using fixed-effects models and by dose of metformin (1,000 vs. 2,000 mg), age of participants (12–19 vs. <12 years), co-intervention (metformin vs. metformin + co-intervention), baseline BMI (mean ≥35 vs. <35 kg/m2), and by excluding one study reporting greater treatment effects than the other studies.[4]

Results

Five studies published between 2001 and 2008 met the inclusion criteria.[4–8] This included one crossover trial.[5]

Three studies took place in the U.S.,[6–8] and one each in Australia[5] and Turkey.[4] All trials lasted 6 months with metformin doses from 1,000–2,000 mg/day. Three studies used lifestyle co-interventions in either trial arms.[4,7,8] Two studies included adolescents (ages 12–19 years),[6,7] one looked at younger children (ages 6–12 years),[6] and the others spanned ages 9–18 years. In the U.S. and Australian studies, a large proportion of participants (45–90%) were from ethnic backgrounds with high prevalence of metabolic syndrome (African American, Hispanic, or Asian). All participants were hyperinsulinemic or insulin resistant. Sample size ranged from 28–120 participants at randomization; in total there were 365 participants and 320 trial completers. Mean attrition rates were 11% in metformin groups and 16% in placebo groups.

In the pooled analysis, metformin reduced BMI by a mean of 1.42 kg/m2 (95% CI 0.83–2.02) compared with placebo (I2 = 56.2%; n = 342) (Fig. 1). Sensitivity analyses did not reveal notable differences by age, dose, or baseline BMI. When the outlier result was excluded, metformin reduced BMI by 1.15 kg/m2 (0.73–1.57, I2 = 0%). Reduction in fasting insulin was greater in metformin than placebo groups in three studies, but evidence for a treatment effect was weak (−5.30 μU/ml [95% CI −11.96 to 1.36], I2 = 78.7%; n = 257).[4–7] Pooled metformin effect on the homeostasis model assessment of insulin resistance (HOMA-IR) score was −2.01 (95% CI −3.26 to −0.75, I2 = 49.5%; n = 234)[4,6,8] and −1.28 (−2.55 to −0.21, I2 = 0%) if the Turkish study was excluded.

Figure 1. Forest plot comparing change in BMI (kg/m2) in metformin and placebo groups.

Figure 1.

Forest plot comparing change in BMI (kg/m2) in metformin and placebo groups.

Pooled mean metformin effect on total cholesterol was −0.19 mmol/l (95% CI −0.38 to −0.01, I2 = 0%; n = 234).[4,6,7] Analyses did not provide strong evidence for a treatment effect on fasting glucose, HDL cholesterol, triglyceride levels, or blood pressure. There was insufficient data to comment on body fat outcomes. Gastrointestinal problems were the most common reported side effect (in 20–30%) and were more frequently reported in metformin than in placebo groups (risk difference 10–14%).[6,7] Only one participant reported gastrointestinal problems as the reason for leaving a study.[7]

Conclusions

Our meta-analysis provides some support for a beneficial metformin effect on obesity outcomes among hyperinsulinemic children and adolescents. Treatment over 6 months may be efficacious in reducing BMI by 1.42 kg/m2 (equivalent to 0.4 SD, based on SD for BMI in U.K. and U.S. adolescents) and HOMA-IR score by 2.01 (~0.6 SD).[9] Metformin use was also associated with a small reduction in total cholesterol level (~0.26 SD),[10] but these are unadjusted measures, and it is not possible to determine whether the effects are secondary to reductions in BMI and HOMA-IR or attributable to other factors. To our knowledge, the effects of metformin on BMI in obese children without diabetes have been synthesized in only one published review based on three studies,[11] which identified no treatment effect at 6 months (−0.17 kg/m2 [95% CI −0.62 to −0.28]).

Metformin may not be as effective as behavioral interventions in reducing BMI: a meta-analysis of behavioral interventions in obese adolescents reported an effect of −3.04 kg/m2 (95% CI −3.14 to −2.94) at 6 months, which was maintained at 12 months follow-up.[12] When compared with drugs that are licensed for obesity, metformin has moderate effect: meta-analyses of RCTs reported an orlistat effect of −0.76 kg/m2 (−1.07 to −0.44) and a sibutramine effect of −1.66 kg/m2 (−1.89 to −1.43) at 6 months.[12]

The results of this review must be interpreted with caution: the studies were short-term and based on small samples; participants were mainly from the U.S., and large portions were from ethnic backgrounds known to be at increased risk of metabolic disorders, limiting the generalizability of findings; and the studies presented unadjusted measures without intention-to-treat analyses, which may have overestimated treatment effects.

Metformin may be efficacious in reducing BMI and insulin resistance among obese hyperinsulinemic children and adolescents in the short term. Larger, long-term studies across different populations are needed to establish the role of metformin as therapy for obesity and cardiometabolic risk in young people.