Monocyte-suppressing effect of high-dose metformin in fenofibrate-treated patients with impaired glucose tolerance

Background: fibrates were found to reduce cytokine release and low-grade inflammation in patients with impaired glucose tolerance. the aim of this study was to investigate whether these effects of fibrates may be potentiated by metformin treatment. methods: the study included 43 patients with isolated impaired glucose tolerance and normal plasma lipids who had been treated for at least 6 months with micronized fenofibrate (200 mg daily). these subjects were randomly assigned to 12 weeks'treatment with either high dose metformin (3 g daily in three divided doses) or placebo. plasma lipids,glucose homeostasis markers,monocyte cytokine release and plasma c-reactive protein levels were determined before randomization and at the end of the treatment. results: metformin treatment reduced plasma c-reactive protein levels and monocyte release of tumor necrosis factor-a and interleukin-6,as well as tended to reduce monocyte release of interleukin-1b and monocyte chemoattractant protein-1,which was accompanied by an improvement in insulin sensitivity. conclusions: our results show that high-dose metformin produces monocyte-suppressing and systemic anti-inflammatory effects in fibrate-treated patients with isolated impaired glucose tolerance. this suggests that fibrate-metformin combination therapy may bring clinical benefits to impaired glucose tolerance patients at high cardiovascular risk.copyright © 2013 by institute of pharmacology polish academy of sciences.