The effects of metformin on infl ammatory mediators in obese adolescents with insulin resistance: Controlled randomized clinical trial

Objective: To compare serum concentrations of infl ammatory cytokines, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor a (TNF α ), before and after 3 months treatment with metformin in obese adolescents with insulin resistance (IR). Design and subjects: This was a randomized, doubleblinded, clinical trial of two groups of obese adolescents with IR, aged 9 - 18 years: a placebo group (n = 14) and a metformin group (n = 12) who received 500 mg metformin every 12 h for 3 months. Anthropometric and biochemical (metabolic and infl ammatory cytokines) assessments were compared at the beginning and end of treatment. Results: After 3 months of treatment, body mass index (kg/m ² ) was reduced in both groups: placebo group (32.82 ± 6.37 - 32.10 ± 6.52; p = 0.011) and metformin group (33.44 ± 5.82 - 32.71 ± 5.77; p = 0.015). Serum fasting insulin concentrations (pmol/L) increased in the placebo group (189.45 ± 112.64 - 266.06 ± 167.79; p = 0.01) and showed a slight decrease in the metformin group (256.82 ± 113.89 - 229.25 ± 86.53; p = 0.64). Adiponectin concentrations ( μ g/mL) decreased in the placebo group (13.17 ± 7.31-5.65 ± 6.69; p = 0.02), while these remained stable in the metformin group (8.57 ± 3.98 - 7.86 ± 6.23; p = 0.64). In the metformin group, signifi cant reductions were found in the variances of serum TNF a concentrations (p = 0.006; Levene test). Conclusion: These results suggest that treating obese adolescents with IR using metformin for 3 months is an option for patients without response to traditional lifestyle change because metformin improves infl ammatory activity, which is an etiological factor in cardiovascular disease development.