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OBJECTIVETo compare extra-lipid effects of statins and fibrates in relation to the baseline metabolic status of patients.RESEARCH DESIGN AND METHODSThe study involved a group of 242 metabolic syndrome patients with or without pre-diabetes and randomized to atorvastatin, fenofibrate, or placebo.RESULTSCompared with matched healthy subjects, metabolic syndrome patients exhibited higher plasma levels/activities of high-sensitivity C-reactive protein (hs-CRP), fibrinogen, factor VII, plasminogen activator inhibitor 1, and enhanced monocyte cytokine release. These abnormalities were alleviated by both atorvastatin and fenofibrate treatment. CRP-lowering and monocyte-suppressing actions were more pronounced for atorvastatin in subjects with impaired fasting glucose and for fenofibrate in patients with impaired glucose tolerance.CONCLUSIONSThe presence of pre-diabetes potentiates metabolic syndrome–induced abnormalities in plasma markers of inflammation and hemostasis and in monocyte secretory function. Both atorvastatin and fenofibrate exhibit multidirectional pleiotropic effects in subjects with metabolic syndrome, the strength of which seem to be partially determined by the type of pre-diabetes.

PurposeThe aim of this study was to compare the effects of fibrates and omega-3 fatty acids on lymphocyte secretory function and systemic inflammation in patients with isolated hypertriglyceridemia.MethodsThe study included 107 patients with isolated hypertriglyceridemia who received bezafibrate (200 mg twice daily), omega-3 fatty acids (1 g twice daily) or placebo for 12 weeks. The lipid profile, fasting and 2-h post-glucose load plasma glucose levels, homeostasis model assessment index (HOMA), plasma high-sensitivity C-reactive protein (hsCRP) levels and lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α were assessed at baseline, on the day of randomization, and after 4 and 12 weeks of treatment.ResultsBoth bezafibrate and omega-3 fatty acids reduced plasma triglyceride levels. Bezafibrate additionally decreased total and low-density lipoprotein-cholesterol levels and the HOMA and insignificantly decreased post-glucose load plasma glucose, as well as increased high-density lipoprotein-cholesterol. Bezafibrate treatment was associated with a reduction in lymphocyte release of interleukin-2, interferon-γ and tumor necrosis factor-α, which was accompanied by a reduction in plasma hsCRP levels. Omega-3 fatty acid did not significantly reduce lymphocyte cytokine release and plasma hsCRP. The anti-inflammatory effects of both drugs did not correlate with their action on plasma lipids, but in the case of the former the effect was related to the improvement in insulin sensitivity.ConclusionOur results indicate that bezafibrate is superior to omega-3 fatty acid in inhibiting systemic inflammation and lymphocyte secretory function.

Abstract: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.

Our results show that high-dose metformin exhibits beneficial effects on coagulation and fibrinolysis in isolated IGT patients treated with a fibrate.