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 (TNFalpha), 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/m2) 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 (microg/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 TNFalpha 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.