Effects of Metformin in Obese Insulin-resistant Children

Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. The objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant.

This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m²) insulin-resistant children aged 6-12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program.

Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference −1.09 kg/m², CI −1.87 to −0.31, P = 0.006), body weight (difference −3.38 kg, CI −5.2 to −1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups −0.07, CI −0.12 to −0.01, P = 0.02), and fat mass (difference −1.40 kg, CI −2.74 to −0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further.

From the results it was concluded that metformin treatment modestly reduces body weight and adiposity and improves measures of glucose homeostasis in obese insulin-resistant 6- to 12-year-old children. Although the weight loss produced is small, metformin treatment may hold promise as a method to prevent or delay the appearance of impaired glucose homeostasis in children at high risk for the development of Type 2 diabetes.