Objective To determine if metformin improves markers of inflammation, thrombosis, and intrahepatic fat contents in children with uncomplicated obesity. Methods Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein (hsCRP) and/or fibrinogen concentrations (>2 standard deviations) were randomized to structured diet/exercise or diet/exercise and metformin for 6 months. Blood samples, dual energy X-ray absorptiometry data, and liver magnetic resonance images were obtained. Results Forty-two of 66 recruited children (7–18 years) completed 6 months. Weight loss was modest but more pronounced in the metformin group (−4.9±1.0 kg) than in the diet/exercise group (−1.7±1.1 kg, p<0.03), whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group. Baseline intrahepatic fat was high but decreased only in the diet/exercise (not metformin) pubertal group. Conclusions Six months of metformin therapy improved weight loss and reduced abdominal adiposity, but did not enhance the beneficial effect of diet and exercise on markers related to inflammation, thrombosis, or hepatic fat in obese children with normal glucose tolerance.

Background: Metabolic syndrome (MS)-related comorbidities in obesity, such as hypertension, dyslipidemia, and glucose intolerance, are increasingly recognized in children, predisposing them to early cardiovascular disease.

Purpose Obesity in adolescence increases the risk for early adult cardiovascular disease. We recently showed that 6 months of diet, exercise, and metformin resulted in reductions in adiposity and that diet/exercise alone reduced proinflammatory factors and intrahepatic fat in pubertal children with uncomplicated obesity. The purpose of the present study was to determine whether changes in cardiorespiratory fitness (CRF) after 6 months of structured diet and exercise (DE) or DE plus metformin are related to the previously observed changes in adiposity, markers of inflammation, and intrahepatic fat. Methods Sixteen obese pubertal adolescents between the ages of 10 and 17 were randomized into a structured lifestyle program consisting of DE or DE plus metformin. Subjects performed aerobic and resistance exercise 3 d·wk−1, 30 min per session. Cycle ergometer maximal oxygen consumption (V̇O2max), body composition, blood markers (glucose, insulin, homeostatic model assessment–insulin resistance, interleukin-6, hsCRP), and intrahepatic fat were measured at baseline and 6 months. Results In the cohort, as whole-body weight decreased by 4.0% (P = 0.009), body mass index decreased by 4.9% (P = 0.003), percent body fat decreased by 8.8% (P < 0.001), and V̇O2max improved in 10 of 16 subjects. The addition of metformin provided no further effect on body composition, CRF, or inflammatory factors. More favorable changes in adiposity, adiponectin, and a trend toward blood glucose and interleukin-6 concentrations (P = 0.07) were observed in subjects who increased V̇O2max at 6 months (n = 10) compared with no change in these variables in those who did not improve V̇O2max. Conclusions Metformin did not provide benefits above lifestyle modification for improving CRF in obese adolescents. Improvements in V̇O2max seem to be associated with more favorable metabolic outcomes.