Pleiotropic Effects of Atorvastatin and Fenofibrate in Metabolic Syndrome and Different Types of Pre-Diabetes

Abstract

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.

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

“…It is possible that the impact of fenofibrate and non-pharmacological treatment on monocyte secretory function and systemic inflammation was stronger than that of fenofibrate alone. In line with this explanation, baseline cytokine release in this study was much lower than in untreated IGT patients, slightly lower than in fenofibrate-treated IGT patients and only moderately elevated if compared with healthy subjects participating in other studies [3,8].…”

“…It should be underlined that fenofibrate administered alone to patients with both overt type 2 diabetes and IGT exhibited strong monocyte-suppressing and systemic anti-inflammatory effects [3,4,8,11]. In the latter group of patients, these effects were observed even though fenofibrate-treated IGT patients did not follow any special dietary regimen [8].…”

“…Similarly, administered to metabolic syndrome patients, fenofibrate not only improved glucose homeostasis (a decrease in fasting and post-challenge plasma glucose, insulin resistance and glycated hemoglobin), but also produced C-reactive protein (CRP)-lowering and monocyte-suppressing effects [3]. In the subgroup of patients with impaired glucose tolerance (IGT), monocyte-suppressing effects of fenofibrate were more prominent than the analogous effects of atorvastatin [3].…”

The Effect of Testosterone and Fenofibrate, Administered Alone or in Combination, on Cardiometabolic Risk Factors in Men with Late‐Onset Hypogonadism and Atherogenic Dyslipidemia

“…Previously, we observed a multidirectional action of fenofibrate including an improvement in glucose metabolism and the inhibitory action on plasma lipids and other risk factors in various metabolic disturbances, including prediabetes, overt diabetes, and mixed dyslipidemia [20][21][22][23][24]. However, the present study is the first which has shown a beneficial effect of any fibrate in patients with hypogonadism.…”

Treatment and impact of dyslipidemia in diabetic nephropathy

“…Statins and fibrates are representative drugs for dyslipidemia. Besides reducing plasma cholesterol levels they are thought to have many pleiotropic effects including improvement of endothelial function and inflammation [3,4]. However, treatment of patients with dyslipidemia is complicated because it is not a simple metabolic disorder but closely related to the patient's lifestyle.…”