Lymphocyte-suppressing and systemic anti-inflammatory effects of high-dose metformin in simvastatin-treated patients with impaired fasting glucose

Objective: No previous study has investigated whether metformin produces any effect on lymphocyte secretory function in patients with glucose metabolism abnormalities. Methods: Sixty-two subjects with impaired fasting glucose (IFG) treated for at least 3 months with simvastatin were allocated into one of two groups receiving, respectively, metformin (3 g daily) or placebo for the following 90 days. Plasma lipids, glucose homeostasis markers, plasma C-reactive protein and intercellular adhesion molecule-1 levels, as well as lymphocyte release of proinflammatory cytokines were determined before randomization and at the end of the treatment. Results: Fifty-eight patients completed the study. Metformin, but not placebo, administered to simvastatin-treated IFG subjects reduced plasma levels of C-reactive protein, soluble intercellular adhesion molecule-1, as well as lymphocyte release of interleukin-2, interferon-gamma and tumor necrosis factor-alpha, which was accompanied by the improvement in insulin sensitivity and a reduction in free fatty acid levels. Conclusions: The obtained results indicate that metformin potentiates lymphocyte-suppressing and systemic anti-inflammatory effects of simvastatin in subjects with IFG. These effects of statin-metformin combination therapy may play a role in the prevention and treatment of atherosclerosis and its complications in patients with early glucose metabolism abnormalities. (C) 2012 Elsevier Ireland Ltd. All rights reserved.