title: A randomized trial of the effect of statin and fibrate therapy on arterial function in CKD. Hemostatic effects of bezafibrate and ω-3 fatty acids in isolated hypertriglyceridemic patients. The effect of bezafibrate and omega-3 fatty acids on lymphocyte cytokine release and systemic inflammation in patients with isolated hypertriglyceridemia Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT). Effect of fenofibrate and niacin on intrahepatic triglyceride content, very low-density lipoprotein kinetics, and insulin action in obese subjects with nonalcoholic fatty liver disease. Proof of concept study: does fenofibrate have a role in sleep apnoea syndrome? Serum insulin-like growth factor-I level is independently associated with coronary artery disease progression in young male survivors of myocardial infarction: beneficial effects of bezafibrate treatment. Effect of gemfibrozil treatment in sulfonylurea-treated patients with noninsulin-dependent diabetes mellitus. Lowering of triglycerides by gemfibrozil affects neither the glucoregulatory nor antilipolytic effect of insulin in Type 2 (non-insulin-dependent) diabetic patients Influence of PPAR-alpha agonist fenofibrate on insulin sensitivity and selected adipose tissue-derived hormones in obese women with type 2 diabetes. Effect of simvastatin and fenofibrate on cytokine release and systemic inflammation in type 2 diabetes mellitus with mixed dyslipidemia. Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Pleiotropic Action of Short-Term Metformin and Fenofibrate Treatment, Combined With Lifestyle Intervention, in Type 2 Diabetic Patients With Mixed Dyslipidemia Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men. Comparison of three treatment approaches to decreasing cardiovascular disease risk in nondiabetic insulin-resistant dyslipidemic subjects. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Gemfibrozil improves insulin sensitivity and flow‐mediated vasodilatation in type 2 diabetic patients
abstract: BACKGROUND Although patients with chronic kidney disease ( CKD ) are at increased risk of cardiovascular disease ( CVD ) , the roles of lipid-modifying therapies in decreasing CVD risk are unclear . Our aim is to compare the effects of statin and fibrate therapy on arterial function as a risk marker of CVD . STUDY DESIGN Double-blind , r and omized , placebo-controlled , parallel-group study . SETTING & PARTICIPANTS Ambulatory patients with stages 3 to 5 CKD . INTERVENTION 6 weeks of atorvastatin , 40 mg/d , or gemfibrozil , 600 mg twice daily , with placebo . OUTCOMES & MEASUREMENTS Primary outcome was arterial function assessed by means of endothelial-dependent flow-mediated dilatation ( FMD ) and small-artery compliance ( C2 ) . Secondary outcomes included endothelial-independent glyceryl trinitrate-mediated dilatation ( GTNMD ) , large-artery compliance ( C1 ) , and levels of lipids , lipoproteins , and oxidized low-density lipoprotein , as well as markers of insulin resistance and inflammation . RESULTS Compared with placebo , atorvastatin significantly decreased low-density lipoprotein ( -52 % ) , triglyceride ( -30 % ) , and oxidized low-density lipoprotein levels ( -41 % ; P < 0.0001 ) . Gemfibrozil significantly decreased triglyceride levels ( -40 % ) and increased high-density lipoprotein levels ( + 20 % ; P < 0.0001 ) . Neither atorvastatin nor gemfibrozil had a significant effect on markers of insulin resistance or inflammation . There was no significant change in FMD , GTNMD , or C1 with either atorvastatin or gemfibrozil . There was improvement in C2 with atorvastatin ( + 1.1 mL/mm Hg x 100 ) compared with placebo ( P = 0.024 ) , but not with gemfibrozil compared with placebo . LIMITATIONS Small sample size leading to inadequate power , short duration of therapy , and use of a heterogeneous group of patients with CKD and dialysis patients . CONCLUSION In patients with advanced CKD , atorvastatin is associated with improvement in dyslipidemia and small-artery stiffness , but not endothelial function .  Gemfibrozil improves dyslipidemia , but has no effect on arterial function This study aim ed to compare the effects of ω-3 fatty acids and fibrate treatment on plasma levels and activities of hemostatic risk factors on glucose and lipid metabolism in subjects with isolated hypertriglyceridemia . Seventy-three subjects with elevated triglyceride levels were allocated into one of the following treatment options : bezafibrate ( 200 mg twice daily ) , ω-3 fatty acids ( 1 g twice daily ) or placebo . Plasma lipids , glucose homeostasis markers ( fasting and 2-h post-glucose load plasma glucose levels and HOMA ) , as well as plasma levels/activities of fibrinogen , factor VII and PAI-1 were determined at baseline , on the day of r and omization , and after 4 and 12 weeks of the treatment . Not only did bezafibrate  improve plasma lipids , but it also increased glucose sensitivity and tended to reduce post-glucose loads of plasma glucose . Except for the reduction in plasma triglycerides , ω-3 fatty acids produced no effect on the lipid profile and insulin sensitivity . Both treatment options reduced , to similar extents , plasma levels of fibrinogen and PAI-1 and factor VII coagulant activity . Our study indicates that , although fibrates exhibit more-pronounced metabolic effects than do ω-3 fatty acids , both these treatment options are equipotent in producing a complex beneficial effect on hemostasis in isolated hypertriglyceridemic subjects Purpose The 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 . Methods The 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 r and omization , and after 4 and 12 weeks of treatment . Results Both 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 . Conclusion Our results indicate that bezafibrate is superior to omega-3 fatty acid in inhibiting systemic inflammation and lymphocyte secretory function BACKGROUND Exaggerated postpr and ial lipemia ( PPL ) is a factor in atherogenesis , involving endothelial dysfunction and enhanced oxidative stress . We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus . METHODS AND RESULTS Twenty patients entered a 3-month , double-blind , placebo-controlled  study . Each subject was studied fasting and after a fatty meal , at baseline , and after 3 months of treatment .  Glucose and lipid profiles were measured over an 8-hour postpr and ial period . Endothelial function ( flow-mediated endothelium-dependent vasodilatation [ FMD ] ) and oxidative stress ( electron paramagnetic resonance spectroscopy ) were measured after fasting and 4 hours postpr and ially . At baseline , both groups exhibited similar PPL and deterioration in endothelial function . After ciprofibrate , fasting and postpr and ial FMD values were significantly higher ( from 3.8+/-1 . 8 % and 1.8+/-1.3 % to 4.8+/-1.1 % and 3.4+/-1.1 % ; P<0.05 ) . This was mirrored by a fall in fasting and postpr and ial triglycerides ( 3 . 1+/-2.1 and 6.6+/-4.1 mmol/L to 1.5+/-0.8 and 2.8+/-1.3 mmol/L , P<0 . 05 ) . Fasting and postpr and ial HDL cholesterol was also elevated ( 0 . 9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 and 1.2+/-0.1 mmol/L , P<0 . 05 ) . There were no changes in total or LDL cholesterol . Fasting and postpr and ial triglyceride enrichment of all lipoproteins was attenuated , with cholesterol depletion of VLDL and enrichment of HDL . There were similar postpr and ial increases in oxidative stress in both groups at baseline , which was significantly attenuated by ciprofibrate ( 0.3+/-0.6 versus 1.5+/-1.1 U , P<0.05 ) . CONCLUSIONS This study demonstrates that fibrate therapy improves fasting and postpr and ial endothelial function in type 2 diabetes . Attenuation of PPL and the associated oxidative stress , with increased HDL cholesterol levels , may be important BACKGROUND Diabetes mellitus , impaired fasting glucose level , or insulin resistance are associated with increased risk of cardiovascular disease . OBJECTIVES To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes . METHODS Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial , a r and omized controlled trial that enrolled 2531 men with coronary heart disease ( CHD ) , a high-density lipoprotein cholesterol level of 40 mg/dL or less ( < /=1.04 mmol/L ) , and a low-density lipoprotein cholesterol level of 140 mg/dL or less ( < /=3.63 mmol/L ) . Subjects received either gemfibrozil ( 1200 mg/d ) or matching placebo and were followed up for an average of 5.1 years . In this article , we report the composite end point ( CHD death , stroke , or myocardial infa rct ion ) . RESULTS Compared with those with a normal fasting glucose level , risk was increased in subjects with known diabetes ( hazard ratio [ HR ] , 1.87 ; 95 % confidence interval [ CI ] , 1.44 - 2.43 ; P = .001 ) and those with newly diagnosed diabetes ( HR , 1.72 ; 95 % CI , 1.10 - 2.68 ; P = .02 ) . In persons without diabetes , a fasting plasma insulin level of 39 micro U/mL or greater ( > /=271 pmol/L ) was associated with a 31 % increased risk of events ( P = .03 ) . Gemfibrozil was effective in persons with diabetes ( risk reduction for composite end point , 32 % ; P = .004 ) . The reduction in CHD death was 41 % ( HR , 0.59 ; 95 % CI , 0.39 - 0.91 ; P = .02 ) . Among individuals without diabetes , gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile ( risk reduction , 35 % ; P = .04 ) . CONCLUSION In men with CHD and a low high-density lipoprotein cholesterol level , gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level CONTEXT Nonalcoholic fatty liver disease is associated with risk factors for cardiovascular disease , particularly increased plasma triglyceride ( TG ) concentrations and insulin resistance . Fenofibrate and extended release nicotinic acid ( Niaspan ) are used to treat hypertriglyceridemia and can affect fatty acid oxidation and plasma free fatty acid concentrations , which influence intrahepatic triglyceride ( IHTG ) content and metabolic function . OBJECTIVE The objective of the study was to determine the effects of fenofibrate and nicotinic acid therapy on IHTG content and cardiovascular risk factors . EXPERIMENTAL DESIGN AND MAIN OUTCOME MEASURES : We conducted a r and omized , controlled trial to determine the effects of fenofibrate ( 8 wk , 200 mg/d ) , Niaspan ( 16 wk , 2000 mg/d ) , or placebo ( 8 wk ) on IHTG content , very low-density lipoprotein ( VLDL ) kinetics , and insulin sensitivity . SETTING AND PARTICIPANTS Twenty-seven obese subjects with nonalcoholic fatty liver disease ( body mass index 36 + /- 1 kg/m(2 ) , IHTG 23 + /- 2 % ) were studied at Washington University . RESULTS Neither fenofibrate nor Niaspan affected IHTG content , but both decreased plasma TG , VLDL-TG , and VLDL-apolipoprotein B concentrations ( P < 0.05 ) . Fenofibrate increased VLDL-TG clearance from plasma ( 33 to 54 ml/min ; P < 0.05 ) but not VLDL-TG secretion .  Niaspan decreased VLDL-TG secretion ( 27 to 15 micromol/min ; P < 0.05 ) without affecting clearance . Both fenofibrate and Niaspan decreased VLDL-apolipoprotein B secretion ( 1.6 to 1.2 and 1.3 to 0.9 nmol/min , respectively ; P < 0.05 ) . Niaspan reduced hepatic , adipose tissue , and muscle insulin sensitivity ( P < 0.05 ) , whereas fenofibrate had no effect on insulin action . CONCLUSIONS Fenofibrate and Niaspan decrease plasma VLDL-TG concentration without altering IHTG content . However , the mechanism responsible for the change in VLDL-TG concentration is different for each drug ; fenofibrate increases plasma VLDL-TG clearance , whereas nicotinic acid decreases VLDL-TG secretion Abstract Objective : To investigate the effect of fenofibrate on  sleep apnoea indices . Methods : Proof-of-concept study comprising a placebo run-in period ( 1 week , 5 weeks if fibrate washout was required ) and a 4-week r and omized , double-blind treatment period . Thirty-four subjects ( mean age 55 years , body mass index 34 kg/m2 , fasting triglycerides 3.5 mmol/L ) with diagnosed sleep apnoea syndrome not treated with continuous positive airways pressure were enrolled and r and omized to once daily treatment with fenofibrate ( 145 mg NanoCrystal ® tablet ) or placebo .  Overnight polysomnography , computerized attention/vigilance tests and blood sampling for measurement of lipids , insulin , fasting plasma glucose and fibrinogen were performed at the end of each study period . Clinical trial registration : NCT00816829 . Main outcome measures : As this was an exploratory study , a range of sleep variables were evaluated . The apnoea/hypopnoea index ( AHI ) and percentage of time spent with arterial oxygen saturation ( SpO2 ) < 90 % were relevant as they have been evaluated in other clinical trials . Other variables included total apnoeas , hypopnoeas and oxygen desaturations , and non-cortical micro-awakenings related to respiratory events per hour . Results : Fenofibrate treatment significantly reduced the percentage of time with SpO2 < 90 % ( from 9.0 % to 3.5 % vs. 10.0 % to 11.5 % with placebo , p = 0.007 ) , although there was no significant change in the AHI ( reduction vs. control 14 % ( 95%CI −47 to 40 % , p = 0.533 ) . Treatment reduced obstructive apnoeas ( by 44 % , from 18.5 at baseline to 15.0 at end of treatment vs. 29.0 to 30.5 on placebo , p = 0.048 ) , and non-cortical micro-awakenings per hour ( from 23.5 to 18.0 vs. 24.0 to 25.0 with placebo , p = 0.004 ) . Other sleep variables were not significantly influenced by fenofibrate . Key limitations : Exploratory study in patients with mild to moderate sleep apnoea , limited treatment duration ; concomitant hypnotic treatment ( 35 % ) ; lack of correction for multiplicity of testing . Conclusions : The consistent direction of change in sleep indices in this proof-of-concept study may support further investigation of fenofibrate in moderate to severe sleep apnoea syndrome OBJECTIVES We investigated whether the effect of bezafibrate on  progression of coronary atherosclerosis  in the BEzafibrate Coronary Atherosclerosis Intervention Trial ( BECAIT ) was related to insulin-like growth factor (IGF)-I and glucose-insulin homeostasis . BACKGROUND BECAIT , the first double-blind , placebo-controlled , r and omized , serial angiographic trial of a fibrate compound , demonstrated that progression of focal coronary atherosclerosis in young patients after infa rct ion could be retarded by bezafibrate treatment . METHODS The treatment effects on serum concentrations of IGF-I and insulin-like growth factor binding protein (IGFBP)-1 , as well as on basal and postload glucose and insulin levels , were examined , and on-trial determinations were related to the angiographic outcome measurements . RESULTS Bezafibrate treatment result ed in a significant reduction of serum IGF-I levels , both at two and five years , and on-trial serum IGF-I levels were directly related to changes in both minimal lumen diameter ( r = 0.25 , p < 0.05 ) and mean segment diameter ( r = 0.29 , p < 0.05 ) . In contrast , none of the available indexes of insulin resistance ( homeostasis model assessment estimate , basal and postload plasma insulin concentrations and serum IGFBP-1 levels ) were related to the angiographic changes , nor were they significantly affected by bezafibrate treatment . Multiple stepwise regression analysis showed that the relation between on-trial serum IGF-I level and coronary artery disease ( CAD ) progression was independent of baseline angiographic score , age , body mass index , serum lipoprotein and plasma fibrinogen concentrations and measures of glucose-insulin homeostasis . CONCLUSIONS IGF-I could be implicated in the progression of premature CAD , and a reduction of serum IGF-I concentration could account partly for the effect of bezafibrate on progression of focal coronary atherosclerosis This study was initiated to 1 ) assess gemfibrozil 's ability to lower plasma triglyceride ( TG ) concentration in patients with NIDDM , and 2 ) determine whether this effect was associated with any changes in glycemic control . Measurements were made of mean hourly plasma glucose , insulin , TG , and FFA concentrations from 1200 - 1600 h in response to a test meal ; hepatic glucose production ( HGP ) ; insulin-stimulated glucose uptake during a hyperinsulinemic glucose clamp study ( MCR ) ; and fasting plasma lipoprotein TG and cholesterol concentrations in 12 patients with NIDDM before and 3 months after gemfibrozil treatment . Although ambient plasma TG and FFA concentrations fell significantly , plasma glucose , insulin , HGP , concentrations fell significantly , plasma glucose , insulin , HGP , and glucose MCR did not change . However , when patients were divided into two groups , those with fasting plasma glucose levels above 9 mmol/L ( fair control ) and those with levels below 9 mmol/L ( good control ) , a different phenomenon was observed . Patients in fair control had significant decreases in mean hourly plasma concentrations of glucose ( 15.1 + /- 1.7 to 12.6 + /- 0.9 mmol/L ; P less than 0.001 ) , insulin ( 523 + /- 59 to 471 + /- 75 pmol/L ; P less than 0.001 ) , FFA ( 652 + /- 150 to 504 + /- 76 mumol/L ) , and HGP ( 9.5 0.4 to 8.1 + /- 0.4 mumol/kg.min ; P less than 0.005 ) , and an increase in glucose MCR ( 2.63 + /- 0.49 to 3.72 + /- 0.54 mL/kg.min ; P less than 0.07 ) in association with a fall in TG from 6.9 + /- 1.3 to 3.5 + /- 0.9 mmol/L ( P less than 0.001 ) . Although fasting low density lipoprotein cholesterol increased ( 1.8 + /- 0.2 to 2.7 + /- 0.2 mmol/L ; P less than 0.05 ) , the ratio of total to high density lipoprotein cholesterol decreased ( 6.84 + /- 0.88 to 5.80 + /- 1.05 ; P less than 0.02 ) . Despite a significant fall in mean hourly TG concentration ( 4.6 + /- 0.7 to 3.8 + /- 0.7 mmol/L ; P less than 0.001 ) , neither insulin , FFA , HGP , nor glucose MCR changed in patients in good control . Furthermore , the mean hourly plasma glucose concentration increased from 9.2 + /- 0.7 to 11.7 + /- 1.4 mmol/L ( P less than 0.001 ) . Low density lipoprotein cholesterol also increased in this group ( 1.9 + /- 0.2 to 2.7 + /- 0.2 mmol/L ; P less than 0.02 ) , but , as before , the ratio of total to high density lipoprotein cholesterol decreased ( 8.15 + /- 1.93 to 6.36 + /- 1.03 ; P less than 0.02 ) Summary Hypertriglyceridaemia and insulin resistance are closely associated but it is unknown whether hypertriglyceridaemia per se contributes to insulin resistance . In the present study we examined whether gemfibrozil , by lowering triglyceride levels , improves the glucoregulatory and antilipolytic action of insulin in Type 2 ( non-insulin-dependent ) diabetes mellitus . Twenty patients were r and omly allocated to receive either placebo or gemfibrozil 1200 mg daily for 12 weeks in a double-blind study . Very low density lipoprotein triglyceride levels decreased in the gemfibrozil group by 42±12 % ( p<0.01 ) . Gemfibrozil had no effect on the diurnal concentration of non-esterified fatty acids ( NEFA ) . At the r and omization HbA1c levels were comparable ( 7.6±0.3 vs 7.8±0.2 % , NS ) and increased slightly both in the gemfibrozil ( 8.2±0.4 % , p<0.05 ) and placebo groups ( 8.0±0.3 % , NS ) . Pre- and post-treatment diurnal glucose and insulin concentrations remained unchanged . Basal pre- and post-treatment hepatic glucose production rates were comparable in both groups and similarly suppressed by insulin . Rate of whole body glucose disposal during a low-dose insulin infusion ( serum insulin ∼90 pmol/l ) ( pre- vs post-gemfibrozil 11.9±1.1 vs 11.1±0.7 , pre- vs post-placebo 9.9±1.1 vs 10.8±0.8 μmol·kg−1·min−1 , NS for both ) and a high-dose insulin infusion ( serum insulin ∼500 pmol/l ) ( 16.2 + -1.7 vs 17.7±2.7 , 17.1±4.2 vs 17.4±2.9 μmol·kg−1·min−1 , respectively , NS for both ) remained unchanged . Basal pre- and post-treatment NEFA turnover rates were comparable in both groups and similarly suppressed by insulin . Also rates of total lipid oxidation , plasma NEFA oxidation and non-oxidative NEFA metabolism remained unchanged in both groups . We conclude that gemfibrozil effectively lowers serum triglycerides but has no effect on insulin sensitivity of glucose and NEFA metabolism . The data suggest that hypertriglyceridaemia is a consequence rather than a cause of insulin resistance in Type 2 diabetic patients PPAR-alpha agonists improve insulin sensitivity in rodent models of obesity/insulin resistance , but their effects on insulin sensitivity in humans are less clear . We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-alpha agonist fenofibrate  and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate . At baseline , body mass index , serum glucose , triglycerides , glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes , while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group ( n=10 ) . No differences were found in serum resistin levels between obese and control group .  Fenofibrate treatment decreased serum triglyceride concentrations , while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration . Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment . All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration . We conclude that administration of PPAR-alpha agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus . The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-alpha expression in human liver and muscle The aim of our study was to compare the effect of simvastatin and fenofibrate treatment on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetes and to assess whether their coadministration is superior to treatment with only 1 of these drugs . One hundred ninety-six adult patients with recently diagnosed and previously untreated type 2 diabetes and mixed dyslipidemia , complying throughout the study with lifestyle intervention and treated with metformin  , were r and omized in a double-blind fashion to receive simvastatin ( 40 mg ) , fenofibrate ( 200 mg ) , simvastatin plus fenofibrate , or placebo for 90 days . Main outcome measurements were monocyte and lymphocyte release of proinflammatory cytokines and plasma levels of C-reactive protein . One hundred ninety patients completed the study . Simvastatin and fenofibrate decreased monocyte release of tumor necrosis factor-α , interleukin-1β , interleukin-6 , and monocyte chemoattractant protein-1 and lymphocyte release of interleukin-2 , interferon-γ , and tumor necrosis factor-α , which was accompanied by a decrease in plasma C-reactive protein levels . Anti-inflammatory effects of fenofibrate partly correlated with the improvement in insulin sensitivity . Lymphocyte-suppressing , but not monocyte-suppressing , effect was stronger if these 2 agents were administered together . In conclusion , simvastatin and fenofibrate exhibit a similar effect on the secretory function of human monocytes and lymphocytes and on systemic inflammation in type 2 diabetic subjects with mixed dyslipidemia . This effect may be clinical ly relevant in the prevention of vascular complications in metformin- and diet-treated subjects with newly diagnosed diabetic dyslipidemia Arteriopathy is the principal complication of type 2 diabetes mellitus . It develops from endothelial dysfunction , which we have hypothesised occurs in diabetes primarily as a consequence of dyslipidaemia and oxidative stress . Fenofibrate and CoQ may improve endothelial function by regulating dyslipidaemia and oxidative stress , respectively . We therefore aim ed to assess the independent and combined effects of fenofibrate and coenzyme Q(10 ) ( CoQ ) on endothelium-dependent and endothelium-independent vasodilator function of the forearm microcirculation in type 2 diabetes . Eighty dyslipidaemic type 2 diabetics were r and omized to receive fenofibrate ( 200 mg/daily ) , CoQ ( 200 mg/daily ) , fenofibrate plus CoQ ( 200 + 200 mg daily ) , or placebo for 12 weeks . Forearm microcirculatory function was assessed with venous occlusion plethysmography during the infusion of acetylcholine ( ACh ) , bradykinin ( BK ) , sodium nitroprusside ( SNP ) and N(G)-monomethyl-L-arginine ( L-NMMA ) into the brachial artery . Blood flow responses were calculated as area under the curve ( AUC ) . Fenofibrate significantly lowered plasma cholesterol , triglyceride and fibrinogen ( P<0.001 ) , and elevated HDL-cholesterol and homocysteine ( P<0.001 ) . CoQ did not change plasma isoprostanes , but significantly lowered systolic blood pressure and HbA(1c ) ( P<0.05 ) . Fenofibrate plus CoQ significantly improved ( P<0.05 ) the AUC for ACh , BK and SNP without significantly altering basal responses to L-NMMA . Fenofibrate or CoQ alone did not significantly alter blood flow responses . Improvements in blood flow were independent of changes in plasma lipids , blood pressure , homocysteine and isoprostanes , but were correlated ( P=0.013 ) with HbA(1c ) . In conclusion , in this factorial trial we found that only the combination of fenofibrate and CoQ markedly improved endothelial and non-endothelial forearm vasodilator function in dyslipidemic type 2 diabetic patients . The favourable vascular effect of this therapeutic combination could be due to increase in the bioactivity of and /or responses to endothelium-derived relaxing factors , including nitric oxide , and this may entail synergistic stimulation of peroxisome proliferator-activated receptors BACKGROUND Omega-3 fatty acids and fenofibrate are both used to treat patients with hypertriglyceridemia .  However , a head-to-head comparison of the lipoprotein and metabolic effects of these two medicines has not been published . METHODS This was a r and omized , single-blind , placebo-controlled , parallel study . Age , sex , and body mass index were matched among groups . All patients were recommended to maintain a low fat diet . Fifty patients in each group were given placebo , omega-3 fatty acids 2 g ( most commonly used dosage in Korean patients ) , or fenofibrate 160 mg , respectively daily for 2 months . RESULTS Omega-3 fatty acids therapy decreased triglycerides by 21 % and triglycerides/HDL cholesterol and improved flow-mediated dilation ( P<0.01 ) , however , did not significantly change insulin , plasma adiponectin levels , and insulin sensitivity ( determined by QUICKI ) relative to baseline measurements . Fenofibrate therapy decreased total cholesterol , triglycerides by 29 % , and triglycerides/HDL-cholesterol ( all P<0.01 ) and improved flow-mediated dilation when compared with baseline . When compared with placebo and omega-3 fatty acids , fenofibrate therapy decreased non-HDL cholesterol ( P<0.001 ) and triglycerides/HDL cholesterol ( P=0.016 ) while increasing HDL cholesterol ( P<0.001 ) and apolipoprotein AI ( P=0.001 ) . Of note , when compared with omega-3 fatty acids , fenofibrate therapy decreased fasting insulin ( P=0.023 ) and increased plasma adiponectin ( P=0.002 ) and insulin sensitivity ( P=0.015 ) . CONCLUSIONS Omega-3 fatty acids and fenofibrate therapy promoted similar changes in triglycerides and endothelium-dependent dilation . However , fenofibrate therapy had substantially better effects on lipoprotein and metabolic profiles in patients with hypertriglyceridemia OBJECTIVE To compare the effect of short-term metformin and fenofibrate treatment , administered alone or in sequence , on glucose and lipid metabolism , cardiovascular risk factors , and monocyte cytokine release in type 2 diabetic patients with mixed dyslipidemia . RESEARCH DESIGN AND METHODS We studied 128 type 2 diabetic patients with mixed dyslipidemia complying throughout the study with lifestyle intervention who were r and omized twice , initially to either  metformin or placebo  , and then to micronized fenofibrate or placebo . RESULTS Fenofibrate alleviated diabetic dyslipidemia – induced changes in plasma high-sensitivity C-reactive protein , fibrinogen , and plasminogen activator inhibitor (PAI)-1 and in monocyte cytokine release , whereas metformin or lifestyle intervention improved mainly glucose and lipid metabolism . The strongest pleiotropic effect was observed when fenofibrate was added to metformin . CONCLUSIONS Fenofibrate , particularly administered together with metformin , is superior to metformin and lifestyle intervention in exhibiting beneficial effects on systemic inflammation , hemostasis , and monocyte secretory function in type 2 diabetic patients with mixed dyslipidemia Obesity is a low grade inflammatory state associated with premature cardiovascular morbidity and mortality . Along with traditional risk factors the measurement of endothelial function , insulin resistance , inflammation and arterial stiffness may contribute to the assessment of cardiovascular risk . We conducted a r and omised placebo controlled trial to assess the effects of 12 weeks treatment with a PPAR alpha agonist ( fenofibrate ) and a PPAR gamma agonist ( pioglitazone ) on these parameters in obese glucose tolerant men .  Arterial stiffness was measured using augmentation index and pulse wave velocity ( PWV ) . E-selectin , VCAM-1 and ICAM-1 were used as markers of endothelial function . Insulin sensitivity improved with pioglitazone treatment ( p=0.001 ) and , in keeping with this , adiponectin increased by 85.2 % ( p<0.001 ) . Pro-inflammatory cytokine levels ( TNFalpha , IL-6 and IL-1 beta ) fell with both treatments ( p<0.01 for TNFalpha and IL-1 beta , p<0.001 for IL-6 ) . VCAM-1 and ICAM-1 were reduced with both treatments ( p<0.001 for VCAM-1 , p<0.05 for ICAM-1 ) and E-selectin improved with pioglitazone treatment ( p=0.05 ) . Both treatments result ed in a fall in augmentation index . PWV fell by 17.4 % with fenofibrate treatment ( p<0.001 ) and 16.3 % with pioglitazone treatment ( p<0.001 ) . Pioglitazone and fenofibrate treatment of obese , glucose tolerant men reduces inflammation , improves markers of endothelial function and reduces arterial stiffness . These results suggest that treatment with PPAR agonists has potential to reduce the incidence of premature cardiovascular disease associated with obesity The efficacy of fenofibrate ( FEN ) , rosiglitazone ( RSG ) , or a calorie-restricted diet ( CRD ) to reduce cardiovascular disease risk was compared in 37 overweight/obese insulin-resistant nondiabetic subjects .  Insulin sensitivity , fasting lipids and lipoproteins , and postpr and ial plasma glucose , insulin , free fatty acid , and triglycerides were measured before and after 3 months of treatment with FEN , RSG , or CRD .  Weight decreased in the CRD group , but did not change significantly after treatment with either drug . Insulin sensitivity improved significantly in the CRD- and RSG-treated groups , but to a greater extent in those administered RSG , without a significant difference comparing FEN treatment with the CRD . Total cholesterol was significantly lower after FEN and CRD treatment . Fasting plasma triglycerides decreased significantly in the FEN- and CRD-treated groups , but postpr and ial concentrations decreased in only FEN-treated subjects . Significant decreases in postpr and ial glucose and insulin were seen in only the RSG- and CRD-treated groups . FEN administration improved dyslipidemia in these subjects without changing insulin sensitivity , whereas insulin sensitivity was enhanced in RSG-treated patients without improvement in dyslipidemia . Weight loss in the CRD group led to improvements in both insulin sensitivity and dyslipidemia , but the change in the former was less than in RSG-treated patients , and improvement in lipid metabolism not as great as with FEN . In conclusion , there did not appear to be 1 therapeutic intervention that effectively treated all metabolic abnormalities present in these patients at greatly increased risk of cardiovascular disease BACKGROUND Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease , partly owing to dyslipidaemia , which can be amenable to fibrate therapy . We design ed the Fenofibrate Intervention and Event Lowering in Diabetes ( FIELD ) study to assess the effect of fenofibrate on cardiovascular disease events in these patients . METHODS We did a multinational , r and omised controlled trial with 9795 participants aged 50 - 75 years , with type 2 diabetes mellitus , and not taking statin therapy at study entry . After a placebo and a fenofibrate run-in phase , we r and omly assigned patients ( 2131 with previous cardiovascular disease and 7664 without ) with a total-cholesterol concentration of 3.0 - 6.5 mmol/L and a total-cholesterol/HDL-cholesterol ratio of 4.0 or more or plasma triglyceride of 1.0 - 5.0 mmol/L to micronised fenofibrate 200 mg daily ( n=4895 ) or matching placebo ( n=4900 ) . Our primary outcome was coronary events ( coronary heart disease death or non-fatal myocardial infa rct ion ) ; the outcome for prespecified subgroup analyses was total cardiovascular events ( the composite of cardiovascular death , myocardial infa rct ion , stroke , and coronary and carotid revascularisation ) . Analysis was by intention to treat . The study was prospect ively registered ( number IS RCT N 64783481 ) . FINDINGS Vital status was confirmed on all but 22 patients . Averaged over the 5 years ' study duration , similar proportions in each group discontinued study medication ( 10 % placebo vs 11 % fenofibrate ) and more patients allocated placebo ( 17 % ) than fenofibrate ( 8 % ; p<0.0001 ) commenced other lipid treatments , predominantly statins . 5.9 % ( n=288 ) of patients on placebo and 5.2 % ( n=256 ) of those on fenofibrate had a coronary event ( relative reduction of 11 % ; hazard ratio [ HR ] 0.89 , 95 % CI 0.75 - 1.05 ; p=0.16 ) . This finding corresponds to a significant 24 % reduction in non-fatal myocardial infa rct ion ( 0.76 , 0.62 - 0.94 ; p=0.010 ) and a non-significant increase in coronary heart disease mortality ( 1.19 , 0.90 - 1.57 ; p=0.22 ) . Total cardiovascular disease events were significantly reduced from 13.9 % to 12.5 % ( 0.89 , 0.80 - 0.99 ; p=0.035 ) . This finding included a 21 % reduction in coronary revascularisation ( 0.79 , 0.68 - 0.93 ; p=0.003 ) . Total mortality was 6.6 % in the placebo group and 7.3 % in the fenofibrate group ( p=0.18 ) . Fenofibrate was associated with less albuminuria progression ( p=0.002 ) , and less retinopathy needing laser treatment ( 5.2%vs 3.6 % , p=0.0003 ) . There was a slight increase in pancreatitis ( 0.5%vs 0.8 % , p=0.031 ) and pulmonary embolism ( 0.7%vs 1.1 % , p=0.022 ) , but no other significant adverse effects . INTERPRETATION Fenofibrate did not significantly reduce the risk of the primary outcome of coronary events . It did reduce total cardiovascular events , mainly due to fewer non-fatal myocardial infa rct ions and revascularisations . The higher rate of starting statin therapy in patients allocated placebo might have masked a moderately larger treatment benefit Background Endothelial dysfunction is an early feature of atherosclerosis . The relationship between insulin action and hypertriglyceridaemia on endothelial function is still debated
target: Conclusion : This meta‐ analysis has shown that fibrate treatment  significantly decreases fasting plasma glucose , insulin levels , and HOMA‐IR indicating additional clinical therapeutic benefits .
background: Aims : The aim of this meta‐ analysis of r and omized placebo‐controlled clinical trials was to assess the effect of fibrates on glycemic parameters .