Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance

OBJECTIVE: Although metformin (MET) is an insulin sensitizer currently used as an adjunct to the treatment of some of the complications of childhood obesity besides type 2 diabetes mellitus, few studies have comprehensively examined its metabolic and clinical effects in obese children with normal glucose tolerance (NGT). METHODS: We therefore conducted a 4-month double-blind clinical trial in 28 obese [mean body mass index (BMI): 40.3 +/- 5.7 kg/m(2)], insulin-resistant [homeostasis model assessment - insulin resistance: 7.6 +/- 2.8 and whole body insulin sensitivity index (WBISI): 1.5 +/- 0.7] adolescents (age 15.0 +/- 1.3 yr) randomized to MET (n = 15, dose 1500 mg daily) or placebo (n = 13). RESULTS: The treatment with MET was well tolerated. MET treatment was associated with a decreased BMI (p = 0.02) as well as with a reduction in subcutaneous fat (p = 0.03), particularly the deep subcutaneous fat (p = 0.04) as assessed by magnetic resonance imaging. Postintervention, the MET group had a 35% improvement in insulin sensitivity (WBISI) compared with the placebo group (p = 0.008). However, significance was lost with adjustments for differences in baseline insulin sensitivity (p = 0.09). While there was no change in inflammatory cytokines or lipid parameters, cardiovascular function as assessed by heart rate recovery after exercise improved with MET and worsened in placebo (p = 0.03). CONCLUSION: Short-term use of MET is well tolerated by obese children with NGT and has a beneficial effect on BMI and autonomic control of the heart as well as a trend toward improved insulin sensitivity. Thus, long-term treatment with MET may provide a means to ameliorate the cardio-metabolic consequences of adolescent obesity.