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.