The effects of metformin on inflammatory mediators in obese adolescents with insulin resistance: controlled randomized clinical trial

Objective: To compare serum concentrations of inflammatory cytokines, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), adiponectin, and tumor necrosis factor alpha (TNF alpha), before and after 3 months treatment with metformin in obese adolescents with insulin resistance (IR). Design and subjects: This was a randomized, double-blinded, 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 inflammatory 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 (mu 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, significant reductions were found in the variances of serum TNF alpha 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 inflammatory activity, which is an etiological factor in cardiovascular disease development.