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Fenofibrate

A Review of its Lipid-Modifying Effects in Dyslipidemia and its Vascular Effects in Type 2 Diabetes Mellitus

American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Fenofibrate is a fibric acid derivative with lipid-modifying effects that are mediated by the activation of peroxisome proliferator-activated receptor-α. Fenofibrate also has a number of nonlipid, pleiotropic effects (e.g. reducing levels of fibrinogen, C-reactive protein, and various pro-inflammatory markers, and improving flow-mediated dilatation) that may contribute to its clinical efficacy, particularly in terms of improving microvascular outcomes.

The beneficial effects of fenofibrate on the lipid profile have been shown in a number of randomized controlled trials. In primary dyslipidemia, fenofibrate monotherapy consistently decreased triglyceride (TG) levels to a significantly greater extent than placebo; significantly greater increases in high-density lipoprotein cholesterol (HDL-C) levels and significantly greater reductions in low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels were also seen in some trials. Monotherapy with fenofibrate or gemfibrozil had generally similar effects on TG and HDL-C levels, although in one trial, TC and LDL-C levels were reduced to a significantly greater extent with fenofibrate than with gemfibrozil. Fenofibrate monotherapy tended to improve TG and HDL-C levels to a significantly greater extent than statin monotherapy in primary dyslipidemia, whereas statin monotherapy decreased LDL-C and TC levels to a significantly greater extent than fenofibrate monotherapy. Fenofibrate also had a beneficial effect on atherogenic dyslipidemia in patients with the metabolic syndrome or type 2 diabetes mellitus, reducing TG levels, tending to increase HDL-C levels, and promoting a shift to larger low-density lipoprotein particles.

In terms of cardiovascular outcomes, fenofibrate did not reduce the risk of coronary heart disease (CHD) events to a greater extent than placebo in patients with type 2 diabetes in the FIELD trial. However, the risk of some nonfatal macrovascular events (e.g. nonfatal myocardial infarction, revascularization) and certain microvascular outcomes (e.g. amputation, first laser therapy for diabetic retinopathy, progression of albuminuria) was reduced to a significantly greater extent with fenofibrate than with placebo. Subgroup analysis revealed a significant reduction in the cardiovascular disease (CVD) event rate among fenofibrate recipients in the subgroup of patients with marked hypertriglyceridemia or marked dyslipidemia at baseline.

In the ACCORD Lipid trial, there were no significant differences between patients with type 2 diabetes and a high risk of CVD events who received fenofibrate plus simvastatin and those who received placebo plus simvastatin for any of the primary or secondary cardiovascular outcomes. However, fenofibrate plus simvastatin was of benefit in patients who had markedly high TG levels and markedly low HDL-C levels at baseline. In addition, fenofibrate plus simvastatin slowed the progression of diabetic retinopathy.

Fenofibrate is generally well tolerated. Common adverse events included increases in transaminase levels that were usually transient, minor, and asymptomatic, and gastrointestinal signs and symptoms.

In conclusion, monotherapy with fenofibrate remains a useful option in patients with dyslipidemia, particularly in atherogenic dyslipidemia characterized by high TG and low HDL-C levels.

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References

  1. World Health Organization. Cardiovascular diseases (CVDs) [online]. Available from URL: http://www.who.int/mediacentre/factsheets/fs317/en/index.html# [Accessed 2011 Apr 7].

  2. National Cholesterol Education Program Expert Panel. Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): final report. Circulation 2002 Dec 17; 106(25): 3143–421.

    Google Scholar 

  3. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol 2008 Apr 15; 51(15): 1512–24.

    Article  PubMed  Google Scholar 

  4. Graham I, Atar D, Borch-Johnsen K, et al. European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Atherosclerosis 2007 Sep; 194(1): 1–45.

    Article  PubMed  CAS  Google Scholar 

  5. Zimmet P. Preventing diabetic complications: a primary care perspective. Diabetes Res Clin Pract 2009 May; 84(2): 107–16.

    Article  PubMed  Google Scholar 

  6. Jones PH. Expert perspective: reducing cardiovascular risk in metabolic syndrome and type 2 diabetes mellitus beyond low-density lipoprotein cholesterol lowering. Am J Cardiol 2008 Dec 22; 102(12A): 41–7L.

    Article  Google Scholar 

  7. Toth PP. Clinical insights from the Fenofibrate Intervention and Event Lowering in Diabetes study: a community practice perspective. Int J Clin Pract 2009 Jun; 63(6): 903–11.

    Article  PubMed  CAS  Google Scholar 

  8. Grundy SM, Cleeman JI, Merz NB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004 Jul 13; 110: 227–39.

    Article  PubMed  Google Scholar 

  9. Abbott Healthcare Products Limited. Lipantil Micro (micronised fenofibrate) 67: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/683/SPC/Lipantil+Micro+67/ [Accessed 2011 Mar 16].

  10. Abbott Healthcare Products Limited. Lipantil Micro (micronised fenofibrate) 200: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/684/SPC/Lipantil+Micro+200/ [Accessed 2011 Mar 16].

  11. Abbott Healthcare Products Limited. Lipantil Micro (micronised fenofibrate) 267: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/2567/SPC/Lipantil+Micro+267/ [Accessed 2011 Mar 16].

  12. Abbott Healthcare Products Limited. Supralip (micronised fenofibrate) 160mg: UK summary of product characteristics [online]. Available from URL: http://www.medicines.org.uk/EMC/medicine/3719/SPC/Supralip+160mg/ [Accessed 2011 Mar 16].

  13. Abbott. Fenofibrate 145 mg film-coated tablet: summary of product characteristics. 2009 Dec.

  14. Sauron R, Wilkins M, Jessent V, et al. Absence of a food effect with a 145 mg nanoparticle fenofibrate tablet formulation. Int J Clin Pharmacol Ther 2006 Feb; 44(2): 64–70.

    PubMed  CAS  Google Scholar 

  15. Arakawa R, Tamehiro N, Nishimaki-Mogami T, et al. Fenofibric acid, an active form of fenofibrate, increases apolipoprotein A-I-mediated high-density lipoprotein biogenesis by enhancing transcription of ATP-binding cassette transporter A1 gene in a liver X receptor-dependent manner. Arterioscler Thromb Vasc Biol 2005 Jun; 25(6): 1193–7.

    Article  PubMed  CAS  Google Scholar 

  16. Schoonjans K, Martin G, Staels B, et al. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr Opin Lipidol 1997 Jun; 8(3): 159–66.

    Article  PubMed  CAS  Google Scholar 

  17. Chapman MJ. Fibrates: therapeutic review. Br J Diabetes Vasc Dis 2006 Jan/Feb; 6(1): 11–9.

    Article  CAS  Google Scholar 

  18. Fruchart J-C. Peroxisome proliferator-activated receptor-alpha (PPARα): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 2009 Jul; 205(1): 1–8.

    Article  PubMed  CAS  Google Scholar 

  19. Fruchart J-C, Duriez P. Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism. Drugs Today (Barc) 2006 Jan; 42(1): 39–64.

    Article  CAS  Google Scholar 

  20. Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARa and PPARγ activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. Embo J 1996 Oct 1; 15(19): 5336–48.

    PubMed  CAS  Google Scholar 

  21. Haubenwallner S, Essenburg AD, Barnett BC, et al. Hypolipidemic activity of select fibrates correlates to changes in hepatic apolipoprotein C-III expression: a potential physiologic basis for their mode of action. J Lipid Res 1995 Dec; 36(12): 2541–51.

    PubMed  CAS  Google Scholar 

  22. Staels B, Vu-Dac N, Kosykh VA, et al. Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase: a potential mechanism for the hypolipidemic action of fibrates. J Clin Invest 1995 Feb; 95(2): 705–12.

    Article  PubMed  CAS  Google Scholar 

  23. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim Biophys Acta 1996 Jul 26; 1302(2): 93–109.

    Article  PubMed  CAS  Google Scholar 

  24. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996 May; 37(5): 907–25.

    PubMed  CAS  Google Scholar 

  25. Guérin M, Bruckert E, Dolphin PJ, et al. Fenofibrate reduces plasma cholesteryl ester transfer from HDL to VLDL and normalizes the atherogenic, dense LDL profile in combined hyperlipidemia. Arterioscler Thromb Vasc Biol 1996 Jun; 16(6): 763–72.

    Article  PubMed  Google Scholar 

  26. Caslake MJ, Packard CJ, Gaw A, et al. Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. Arterioscler Thromb 1993 May; 13(5): 702–11.

    Article  PubMed  CAS  Google Scholar 

  27. Ikewaki K, Tohyama J, Nakata Y, et al. Fenofibrate effectively reduces remnants, and small dense LDL, and increases HDL particle number in hypertriglyceridemic men: a nuclear magnetic resonance study. J Atheroscler Thromb 2004; 11(5): 278–85.

    Article  PubMed  CAS  Google Scholar 

  28. Winkler K, Weltzien P, Friedrich I, et al. Qualitative effect of fenofibrate and quantitative effect of atorvastatin on LDL profile in combined hyperlipidemia with dense LDL. Exp Clin Endocrinol Diabetes 2004 May; 112(5): 241–7.

    Article  PubMed  CAS  Google Scholar 

  29. Berthou L, Duverger N, Emmanuel F, et al. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apolipoprotein A-I transgenic mice. J Clin Invest 1996; 97(11): 2408–16.

    Article  PubMed  CAS  Google Scholar 

  30. Vu-Dac N, Schoonjans K, Kosykh V, et al. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor. J Clin Invest 1995; 96: 741–50.

    Article  PubMed  CAS  Google Scholar 

  31. Chinetti G, Gbaguidi FG, Griglio S, et al. CLA-1/SR-BI is expressed in atherosclerotic lesion macrophages and regulated by activators of peroxisome proliferator-activated receptors. Circulation 2000 May 23; 101(20): 2411–7.

    Article  PubMed  CAS  Google Scholar 

  32. Forcheron F, Cachefo A, Thevenon S, et al. Mechanisms of the triglyceride- and cholesterol-lowering effect of fenofibrate in hyperlipidemic type 2 diabetic patients. Diabetes 2002 Dec; 51(12): 3486–91.

    Article  PubMed  CAS  Google Scholar 

  33. Ji J, Barrett PHR, Johnson AG, et al. Lipid transfer proteins and apolipoprotein B-100 metabolism in the metabolic syndrome treated with fenofibrate [abstract no. P11: 111]. Atherosclerosis 2006 Jun; 7 (3 Suppl.): 370.

    Google Scholar 

  34. Kiyanagi T, Miyazaki T, Kume A, et al. Decrease in CETP activity by fenofibrate may increase LDL particle size measured by HPLC method in patients with coronary artery disease [abstract no. P16: 301]. Atherosclerosis 2006 Jun; 7 (3 Suppl.): 559.

    Google Scholar 

  35. McPherson R, Agnani G, Lau P, et al. Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer: studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy. Arterioscler Thromb Vasc Biol 1996 Nov; 16(11): 1340–6.

    Article  PubMed  CAS  Google Scholar 

  36. Bertolini S, Elicio N, Daga A, et al. Effect of a single daily dose treatment of fenofibrate on plasma lipoproteins in hyperlipoproteinaemia IIb. Eur J Clin Pharmacol 1988; 34: 25–8.

    Article  PubMed  CAS  Google Scholar 

  37. Elisaf M, Tsimichodimos V, Bairaktari E, et al. Effect of micronized fenofibrate and losartan combination on uric acid metabolism in hypertensive patients with hyperuricemia. J Cardiovasc Pharmacol 1999 Jul; 34(1): 60–3.

    Article  PubMed  CAS  Google Scholar 

  38. Genest J, Nguyen N-H, Theroux P, et al. Effect of micronized fenofibrate on plasma lipoprotein levels and hemostatic parameters of hypertriglyceridemic patients with low levels of high-density lipoprotein cholesterol in the fed and fasted state. J Cardiovasc Pharmacol 2000 Jan; 35(1): 164–72.

    Article  PubMed  CAS  Google Scholar 

  39. Haak T, Haak E, Kusterer K, et al. Fenofibrate improves microcirculation in patients with hyperlipidemia. Eur J Med Res 1998 Feb 21; 3(1–2): 50–4.

    PubMed  CAS  Google Scholar 

  40. Insua A, Massari F, Rodríguez Moncalvo JJ, et al. Fenofibrate or gemfibrozil for treatment of types IIa and IIb primary hyperlipoproteinemia: a randomized, double-blind, crossover study. Endocr Pract 2002 Mar/Apr; 8(2): 96–101.

    PubMed  Google Scholar 

  41. Kiortsis DN, Millionis H, Bairaktari E, et al. Efficacy of combination of atorvastatin and micronised fenofibrate in the treatment of severe mixed hyperlipidemia. Eur J Clin Pharmacol 2000 Dec; 56(9–10): 631–5.

    Article  CAS  Google Scholar 

  42. Ko HS, Kim CJ, Ryu WS. Effect of fenofibrate on lipoprotein(a) in hypertriglyceridemic patients: impact of change in triglyceride level and liver function. J Cardiovasc Pharmacol 2005 Oct; 46(4): 405–11.

    Article  PubMed  CAS  Google Scholar 

  43. Koh K, Ahn JY, Han SH, et al. Effects of fenofibrate on lipoproteins, vasomotor function, and serological markers of inflammation, plaque stabilization, and hemostasis. Atherosclerosis 2004 Jun; 174(2): 379–83.

    Article  CAS  Google Scholar 

  44. Koh KK, Han SH, Quon MJ, et al. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005 Jun; 28(6): 1419–24.

    Article  PubMed  CAS  Google Scholar 

  45. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005 May 17; 45(10): 1649–53.

    Article  PubMed  CAS  Google Scholar 

  46. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic hypertensive patients. Diabetes Care 2006 Feb; 29(2): 195–201.

    Article  PubMed  CAS  Google Scholar 

  47. Koh KK, Quon MJ, Lim S, et al. Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia. Atherosclerosis 2011; 214(1): 144–7.

    Article  PubMed  CAS  Google Scholar 

  48. Krempf M, Rohmer V, Farnier M, et al. Efficacy and safety of micronised fenofibrate in a randomised double-blind study comparing four doses from 200 mg to 400 mg daily with placebo in patients with hypercholesterolemia. Diabetes Metab 2000 May; 26(3): 184–91.

    PubMed  CAS  Google Scholar 

  49. Lemieux I, Salomon H, Després J-P. Contribution of apo CIII reduction to the greater effect of 12-week micronized fenofibrate than atorvastatin therapy on triglyceride levels and LDL size in dyslipidemic patients. Ann Med 2003; 35(6): 442–8.

    Article  PubMed  CAS  Google Scholar 

  50. Malik J, Melenovsky V, Wichterle D, et al. Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial: FAT). Cardiovasc Res 2001 Nov; 52(2): 290–8.

    Article  PubMed  CAS  Google Scholar 

  51. Paragh G, Seres I, Harangi M, et al. The effect of micronised fenofibrate on paraoxonase activity in patients with coronary heart disease. Diabetes Metab 2003 Dec; 29(6): 613–8.

    Article  PubMed  CAS  Google Scholar 

  52. Rašlová K, Dubovská D, Mongiellová V, et al. Relationship between plasma fenofibric acid levels and the effect of micronized fenofibrate on cholesterol, low-density-lipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia. Eur J Clinc Pharmacol 1997; 52(2): 101–6.

    Article  Google Scholar 

  53. Sasaki J, Yamamoto K, Ageta M. Effects of fenofibrate on high-density lipoprotein particle size in patients with hyperlipidemia: a randomized, double-blind, placebo-controlled, multicenter, crossover study. Clin Ther 2002 Oct; 24(10): 1614–26.

    Article  PubMed  CAS  Google Scholar 

  54. Tsimihodimos V, Kostoula A, Kakafika A, et al. Effect of fenofibrate on serum inflammatory markers in patients with high triglyceride values. J Cardiovasc Pharmacol Ther 2004 Mar; 9(1): 27–33.

    Article  PubMed  CAS  Google Scholar 

  55. Tsimihodimos V, Tambaki A, Tzovaras V, et al. Comparison of the effects of atorvastatin and fenofibrate on apolipoprotein B-containing lipoprotein subfractions in patients with combined dyslipidemia. Hellenic J Cardiol 2004; 45(4): 225–30.

    Google Scholar 

  56. Belfort R, Berria R, Cornell J, et al. Fenofibrate reduces systemic inflammation markers independent of its effects on lipid and glucose metabolism in patients with the metabolic syndrome. J Clin Endocrinol Metab 2010 Feb; 95(2): 829–36.

    Article  PubMed  CAS  Google Scholar 

  57. Chan DC, Watts GF, Ooi EMM, et al. Regulatory effects of fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II kinetics in the metabolic syndrome. Diabetes Care 2009 Nov; 32(11): 2111–3.

    Article  PubMed  CAS  Google Scholar 

  58. Chan DC, Watts GF, Ooi EMM, et al. Atorvastatin and fenofibrate have comparable effects on VLDL-apolipoprotein C-III kinetics in men with the metabolic syndrome. Arterioscler Thromb Vasc Biol 2008 Oct; 28(10): 1831–7.

    Article  PubMed  CAS  Google Scholar 

  59. Krysiak R, Gdula-Dymek A, Bachowski R, et al. Pleiotropic effects of atorvastatin and fenofibrate in metabolic syndrome and different types of pre-diabetes. Diabetes Care 2010 Oct; 33(10): 2266–70.

    Article  PubMed  Google Scholar 

  60. Rosenson RS, Wolff DA, Huskin AL, et al. Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome. Diabetes Care 2007 Aug; 30(8): 1945–51.

    Article  PubMed  CAS  Google Scholar 

  61. Watts GF, Barrett PHR, Ji J, et al. Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome. Diabetes 2003 Mar; 52: 803–11.

    Article  PubMed  CAS  Google Scholar 

  62. Watts GF, Ji J, Chan DC, et al. Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome. Clin Sci (Lond) 2006 Sep; 111(3): 193–9.

    Article  CAS  Google Scholar 

  63. Athyros VG, Papageorgiou AA, Athyrou VV, et al. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 2002 Jul; 25(7): 1198–202.

    Article  PubMed  CAS  Google Scholar 

  64. Cavallero E, Dachet C, Assadolahi F, et al. Micronized fenofibrate normalizes the enhanced lipidemic response to a fat load in patients with type 2 diabetes and optimal glucose control. Atherosclerosis 2003 Jan; 166(1): 151–61.

    Article  PubMed  CAS  Google Scholar 

  65. Feher MD, Caslake M, Foxton J, et al. Atherogenic lipoprotein phenotype in type 2 diabetes: reversal with micronised fenofibrate. Diabetes Metab Res Rev 1999 Nov–Dec; 15(6): 395–9.

    Article  PubMed  CAS  Google Scholar 

  66. Hiukka A, Leinonen E, Jauhiainen M, et al. Long-term effects of fenofibrate on VLDL and HDL subspecies in participants with type 2 diabetes mellitus. Diabetologia 2007 Oct; 50(10): 2067–75.

    Article  PubMed  CAS  Google Scholar 

  67. Playford DA, Watts GF, Best JD, et al. Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetes mellitus. Am J Cardiol 2002 Dec 1; 90: 1254–7.

    Article  PubMed  CAS  Google Scholar 

  68. Zambon A, Gervois P, Pauletto P, et al. Modulation of hepatic inflammation risk markers of cardiovascular diseases by PPAR-α activators: clinical and experimental evidence. Arterioscler Throm Vasc Biol 2006 May; 26(5): 977–86.

    Article  CAS  Google Scholar 

  69. Saougos VG, Tambaki AP, Kalogirou M, et al. Differential effect of hypolipidemic drugs on lipoprotein-associated phospholipase A2. Arterioscler Thromb Vasc Biol 2007 Oct; 27(10): 2236–43.

    Article  PubMed  CAS  Google Scholar 

  70. Rosenson RS. Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome. Am Heart J 2008 Mar; 155(3): 499.e9–16.

    Article  PubMed  CAS  Google Scholar 

  71. Wang TD, Chen WJ, Lin JW, et al. Efficacy of fenofibrate and simvastatin on endothelial function and inflammatory markers in patients with combined hyperlipidemia: relations with baseline lipid profiles. Atherosclerosis 2003 Oct; 170(2): 315–23.

    Article  PubMed  CAS  Google Scholar 

  72. Milionis HJ, Papakostas J, Kakafika A, et al. Comparative effects of atorvastatin, simvastatin, and fenofibrate on serum homocysteine levels in patients with primary hyperlipidaemia. J Clin Pharmacol 2003 Aug; 43(8): 825–30.

    Article  PubMed  CAS  Google Scholar 

  73. Yesilbursa D, Serdar A, Saltan Y, et al. The effect of fenofibrate on serum paraoxonase activity and inflammatory markers in patients with combined hyperlipidemia. Kardiol Pol 2005 Jun; 62(6): 526–30.

    PubMed  Google Scholar 

  74. Oki K, Koide J, Nakanishi S, et al. Fenofibrate increases high molecular weight adiponectin in subjects with hypertriglyceridemia. Endocr J 2007 Jun; 54(3): 431–5.

    Article  PubMed  CAS  Google Scholar 

  75. Krysiak R, Stachura-Kułach A, Okopień B. Metabolic and monocyte-suppressing actions of fenofibrate in patients with mixed dyslipidemia and early glucose metabolism disturbances. Pharmacol Rep 2010 Jan–Feb; 62(1): 120–30.

    PubMed  CAS  Google Scholar 

  76. Idzior-Walus B, Sieradzki J, Rostworowski W, et al. Effects of comicronised fenofibrate on lipid and insulin sensitivity in patients with polymetabolic syndrome X. Eur J Clin Invest 2000 Oct; 30(10): 871–8.

    Article  PubMed  CAS  Google Scholar 

  77. Hamilton SJ, Chew GT, Davis TME, et al. Fenofibrate improves endothelial function in the brachial artery and forearm resistance arterioles of statin-treated type 2 diabetic patients. Clin Sci (Colch) 2010 May; 118(10): 607–15.

    Article  CAS  Google Scholar 

  78. Okopien B, Cwalina L, Lebek M, et al. Effects of fibrates on plasma prothrombotic activity in patients with type IIb dyslipidemia. Int J Clin Pharmacol Ther 2001 Dec; 39(12): 551–7.

    PubMed  CAS  Google Scholar 

  79. Ramjattan BR, Callaghan DJG, Theiss U. Efficacy and tolerability of a ‘suprabioavailable’ formulation of fenofibrate in patients with dyslipidemia: a pooled analysis of two open-label trials. Clin Ther 2002 Jul; 24(7): 1105–16.

    Article  PubMed  CAS  Google Scholar 

  80. Saklamaz A, Comlekci A, Temiz A, et al. The beneficial effects of lipid-lowering drugs beyond lipid-lowering effects: a comparative study with pravastatin, atorvastatin, and fenofibrate in patients with type IIa and type IIb hyperlipidemia. Metabolism 2005 May; 54(5): 677–81.

    Article  PubMed  CAS  Google Scholar 

  81. Staels B, Koenig W, Habib A, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature 1998 Jun 25; 393(6687): 790–3.

    Article  PubMed  CAS  Google Scholar 

  82. Coban E, Ozdogan M, Yazicioglu G, et al. The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidaemic hypertensive patients. Int J Clin Pract 2005 Apr; 59(4): 415–8.

    Article  PubMed  CAS  Google Scholar 

  83. Undas A, Celinska-Löwenhoff M, Domagala TB, et al. Early antithrombotic and anti-inflammatory effects of simvastatin versus fenofibrate in patients with hypercholesterolemia. Thromb Haemost 2005 Jul; 94(1): 193–9.

    PubMed  CAS  Google Scholar 

  84. Ye P, Li J-J, Su G, et al. Effects of fenofibrate on inflammatory cytokines and blood pressure in patients with hypertriglyceridemia [letter]. Clin Chim Acta 2005 Jun; 356(1): 229–32.

    Article  PubMed  CAS  Google Scholar 

  85. Okopień B, Kowalski J, Krysiak R, et al. Monocyte suppressing action of fenofibrate. Pharmacol Rep 2005 May–Jun; 57(3): 367–72.

    PubMed  Google Scholar 

  86. Yang T-L, Chen M-F, Xia X, et al. Effect of fenofibrate on the level of asymmetric dimethylarginine in individuals with hypertriglyceridemia. Eur J Clin Pharmacol 2006 Mar; 62(3): 179–84.

    Article  PubMed  CAS  Google Scholar 

  87. Kowalski J, Okopień B, Madej A, et al. Effects of fenofibrate and simvastatin on plasma sICAM-1 and MCP-1 concentrations in patients with hyperlipoproteinemia. Int J Clin Pharmacol Ther 2003 Jun; 41(6): 241–7.

    PubMed  CAS  Google Scholar 

  88. Okopien B, Krysiak R, Haberka M, et al. Effect of monthly atorvastatin and fenofibrate treatment on monocyte chemoattractant protein-1 release in patients with primary mixed dyslipidemia. J Cardiovasc Pharmacol 2005 Apr; 45(4): 314–20.

    Article  PubMed  CAS  Google Scholar 

  89. Kowalski J, Okopien B, Madej A, et al. Effects of atorvastatin, simvastatin, and fenofibrate therapy on monocyte chemoattractant protein-1 secretion in patients with hyperlipidemia. Eur J Clin Pharmacol 2003 Jul; 59(3): 189–93.

    Article  PubMed  CAS  Google Scholar 

  90. Mackness MI, Phuntuwate W, Suthisisang C, et al. Effect of fenofibrate treatment on paraoxonase 1 [abstract no. A68]. Diabet Med 2006 Mar 1; 23 Suppl. 2: 18–9.

    Article  Google Scholar 

  91. Phuntuwate W, Suthisisang C, Koanantakul B, et al. Effect of fenofibrate therapy on paraoxonase1 status in patients with low HDL-C levels. Atherosclerosis 2008 Jan; 196(1): 122–8.

    Article  PubMed  CAS  Google Scholar 

  92. Capell WH, DeSouza CA, Poirier P, et al. Short-term triglyceride lowering with fenofibrate improves vasodilator function in subjects with hypertriglyceridemia. Arterioscler Thromb Vasc Biol 2003 Feb 1; 23(2): 307–13.

    Article  PubMed  CAS  Google Scholar 

  93. Ellen RL, McPherson R. Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol 1998 Feb 26; 81(4A): 60–5B.

    Article  Google Scholar 

  94. Noguchi Y, Tatsuno I, Suyama K, et al. Effect of fenofibrate on uric acid metabolism in Japanese hyperlipidemic patients. J Atheroscler Thromb 2004; 11(6): 335–40.

    Article  PubMed  CAS  Google Scholar 

  95. Bissonnette R, Treacy E, Rozen R, et al. Fenofibrate raises plasma homocysteine levels in the fasted and fed states. Atherosclerosis 2001 Apr; 155(2): 455–62.

    Article  PubMed  CAS  Google Scholar 

  96. Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate [letter]. Lancet 1999 Jul 17; 354(9174): 219–20.

    Article  PubMed  CAS  Google Scholar 

  97. de Lorgeril M, Salen P, Paillard F, et al. Lipid-lowering drugs and homocysteine [letter]. Lancet 1999 Jan 16; 353(9148): 209–10.

    Article  PubMed  Google Scholar 

  98. Westphal S, Dierkes J, Luley C. Effects of fenofibrate and gemfibrozil on plasma homocysteine [letter]. Lancet 2001 Jul 7; 358(9275): 39–40.

    Article  PubMed  CAS  Google Scholar 

  99. Rosenson RS. Effect of fenofibrate on adiponectin and inflammatory biomarkers in metabolic syndrome patients. Obesity 2009 Mar; 17(3): 504–9.

    Article  PubMed  CAS  Google Scholar 

  100. Rosenson RS, Helenowski IB. Fenofibrate abrogates postprandial blood viscosity among hypertriglyceridemia subjects with the metabolic syndrome. Diabetes Metab Syndr Clin Res Rev 2009; 3(1): 17–23.

    Article  Google Scholar 

  101. Wu T-J, Ou H-Y, Chou C-W, et al. Decrease in inflammatory cardiovascular risk markers in hyperlipidemic diabetic patients treated with fenofibrate. Ann Clin Lab Sci 2007; 37(2): 158–66.

    PubMed  CAS  Google Scholar 

  102. Genest J, Frohlich J, Steiner G. Effect of fenofibrate-mediated increase in plasma homocysteine on the progression of coronary artery disease in type 2 diabetes mellitus. Am J Cardiol 2004 Apr 1; 93(7): 848–53.

    Article  PubMed  CAS  Google Scholar 

  103. Tomizawa A, Hattori Y, Inoue T, et al. Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation. Metabolism 2011 Apr; 60(4): 513–22.

    Article  PubMed  CAS  Google Scholar 

  104. Okayasu T, Tomizawa A, Suzuki K, et al. PPARα activators upregulate eNOS activity and inhibit cytokine-induced NF-κB activation through AMP-activated protein kinase activation. Life Sci 2008 Apr 9; 82(15–16): 884–91.

    Article  PubMed  CAS  Google Scholar 

  105. Kim J, Ahn J-H, Kim J-H, et al. Fenofibrate regulates retinal endothelial cell survival through the AMPK signal transduction pathway. Exp Eye Res 2007 May; 84(5): 886–93.

    Article  PubMed  CAS  Google Scholar 

  106. Varet J, Vincent L, Mirshahi P, et al. Fenofibrate inhibits angiogenesis in vitro and in vivo. Cell Mol Life Sci 2003 Apr; 60(4): 810–9.

    Article  PubMed  CAS  Google Scholar 

  107. Bergman AJ, Murphy G, Burke J, et al. Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. J Clin Pharmacol 2004 Sep; 44(9): 1054–62.

    Article  PubMed  CAS  Google Scholar 

  108. Martin PD, Dane AL, Schneck DW, et al. An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers. Clin Ther 2003 Feb; 25(2): 459–71.

    Article  PubMed  CAS  Google Scholar 

  109. Whitfield LR, Porcari AR, Alvey C, et al. Effect of gemfibrozil and fenofibrate on the pharmacokinetics of atorvastatin. J Clin Pharmacol 2011 Mar; 51(3): 378–88.

    Article  PubMed  CAS  Google Scholar 

  110. Davidson MH. Statin/fibrate combination in patients with metabolic syndrome or diabetes: evaluating the risks of pharamcokinetic drug interactions. Expert Opin Drug Saf 2006; 5(1): 145–56.

    Article  PubMed  CAS  Google Scholar 

  111. Gustavson LE, Schweitzer SM, Koehne-Voss S, et al. The effects ofmultiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3α-hydroxy isomeric metabolite. J Clin Pharmacol 2005 Aug; 45(8): 947–53.

    Article  PubMed  CAS  Google Scholar 

  112. Pan WJ, Gustavson LE, Achari R, et al. Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol 2000; 40: 316–23.

    Article  PubMed  CAS  Google Scholar 

  113. Gustavson LE, Schweitzer SM, Burt DA, et al. Evaluation of the potential for pharmacokinetic interaction between fenofibrate and ezetimibe: a phase I, open-label, multiple-dose, three-period crossover study in healthy subjects. Clin Ther 2006 Mar; 28(3): 373–87.

    Article  PubMed  CAS  Google Scholar 

  114. Kosoglou T, Statkevich P, Fruchart J-C, et al. Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe. Curr Med Res Opin 2004 Aug; 20(8): 1197–207.

    Article  PubMed  CAS  Google Scholar 

  115. Jones MR, Baker BA, Mathew P. Effect of colesevelam HCl on single-dose fenofibrate pharmacokinetics. Clin Pharmacokinet 2004; 43(13): 943–50.

    Article  PubMed  CAS  Google Scholar 

  116. Kajosaari LI, Backman JT, Neuvonen M, et al. Lack of effect of bezafibrate and fenofibrate on the pharmacokinetics and pharmacodynamics of repaglinide. Br J Clin Pharmacol 2004 Oct; 58(4): 390–6.

    Article  PubMed  CAS  Google Scholar 

  117. Boissonnat P, Salen P, Guidollet J, et al. The long-term effects of the lipid-lowering agent fenofibrate in hyperlipidemic heart transplant recipients. Transplantation 1994 Jul; 58(2): 245–7.

    PubMed  CAS  Google Scholar 

  118. Jellinger PS. The American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of dyslipidemia and prevention of atherogenesis 2002 amended version. Endocr Pract 2000 Mar/Apr; 6(2): 162–213.

    PubMed  CAS  Google Scholar 

  119. Levin A, Duncan L, Djurdjev O, et al. A randomized placebo-controlled double-blind trial of lipid-lowering strategies in patients with renal insufficiency: diet modification with or without fenofibrate. Clin Nephrol 2000 Feb; 53(2): 140–6.

    PubMed  CAS  Google Scholar 

  120. Duez H, Lefebvre B, Poulain P, et al. Regulation of human apoA-I by gemfibrozil and fenofibrate through selective peroxisome proliferator-activated receptor a modulation. Arterioscler Thromb Vasc Biol 2005 Mar; 25(3): 585–91.

    Article  PubMed  CAS  Google Scholar 

  121. Després J-P, Lemieux I, Salomon H, et al. Effects of micronized fenofibrate versus atorvastatin in the treatment of dyslipidaemic patients with low plasma HDL-cholesterol levels: a 12- week randomized trial. J Intern Med 2002 Jun; 251(6): 490–9.

    Article  PubMed  Google Scholar 

  122. Ducobu J, Van Haelst L, Salomon H. Comparison of micronized fenofibrate and pravastatin in patients with primary hyperlipidemia. J Cardiovasc Pharmacol 2003; 41(1): 60–7.

    Article  PubMed  CAS  Google Scholar 

  123. Farnier M, Bonnefous F, Debbas N, et al. Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia. Arch Intern Med 1994 Feb 28; 154: 441–9.

    Article  PubMed  CAS  Google Scholar 

  124. Steinmetz A, Schwartz T, Hehnke U, et al. Multicenter comparison of micronized fenofibrate and simvastatin in patients with primary type IIA or IIB hyperlipoproteinemia. J Cardiovasc Pharmacol 1996 Apr; 27(4): 563–70.

    Article  PubMed  CAS  Google Scholar 

  125. Ansquer J-C, Corda C, Le Malicot K, et al. Effects of atorvastatin 10mg and fenofibrate 200 mg on the low-density lipoprotein profile in dyslipidemic patients: a 12-week, multicenter, randomized, open-label, parallel-group study. Curr Ther Res Clin Exp 2009 Apr; 70(2): 71–93.

    Article  CAS  Google Scholar 

  126. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005 Nov 26; 366(9500): 1849–61.

    Article  PubMed  CAS  Google Scholar 

  127. Diabetes Atherosclerosis Intervention Study Investigators. Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study, a randomised study. Lancet 2001 Mar 24; 357(9260): 905–10.

    Article  Google Scholar 

  128. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010 Apr 29; 362(17): 1563–74.

    Article  PubMed  Google Scholar 

  129. Steiner G. The Diabetes Atherosclerosis Intervention Study (DAIS): a study conducted in cooperation with the World Health Organization. Diabetologia 1996 Dec; 39(12): 1655–61.

    Article  PubMed  CAS  Google Scholar 

  130. ACCORD Study Group. Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial: design and methods. Am J Cardiol 2007 Jun 18; 99(12A): 21i–33i.

    Google Scholar 

  131. Chew EY, Ambrosius WT, Davis MD, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010 Jul 15; 363(3): 233–44.

    Article  PubMed  CAS  Google Scholar 

  132. Muhlestein JB, May HT, Jensen JR, et al. The reduction of inflammatory biomarkers by statin, fibrate, and combination therapy among diabetic patients with mixed dyslipidemia: the DIACOR (Diabetes and Combined Lipid Therapy Regimen) study. J Am Coll Cardiol 2006 Jul 18; 48(2): 396–401.

    Article  PubMed  CAS  Google Scholar 

  133. Durrington PN, Tuomilehto J, Hamann A, et al. Rosuvastatin and fenofibrate alone and in combination in type 2 diabetes patients with combined hyperlipidaemia. Diabetes Res Clin Pract 2004 May; 64(2): 137–51.

    Article  PubMed  CAS  Google Scholar 

  134. Keech AC, Mitchell P, Summanen PA, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial. Lancet 2007 Nov 17; 370(9600): 1687–97.

    Article  PubMed  CAS  Google Scholar 

  135. Rajamani K, Colman PG, Li LP, et al. Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 2009 May 23; 373(9677): 1780–8.

    Article  PubMed  CAS  Google Scholar 

  136. Simes J, Voysey M, O’Connell R, et al. A novel method to adjust efficacy estimates for uptake of other active treatments in long-term clinical trials. PLoS One 2010 Jan; 5(1): e8580.

    Article  PubMed  CAS  Google Scholar 

  137. Scott R, O’Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care 2009 Mar; 32(3): 493–8.

    Article  PubMed  CAS  Google Scholar 

  138. Burgess DC, Hunt D, Li L, et al. Incidence and predictors of silent myocardial infarction in type 2 diabetes and the effect of fenofibrate: an analysis from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Eur Heart J 2010 Jan; 31(1): 92–9.

    Article  PubMed  Google Scholar 

  139. Davis TME, Ting R, Best JD, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 2011; 54(2): 280–90.

    Article  PubMed  CAS  Google Scholar 

  140. Drury PL, Ting R, Zannino D, et al. Estimated glomerular filtration rate and albuminuria are independent predictors of cardiovascular events and death in type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetologia 2011 Jan; 54(1): 32–43.

    Article  PubMed  CAS  Google Scholar 

  141. Ansquer J-C, Foucher C, Rattier S, et al. Fenofibrate reduces progression to microalbuminuria over 3 years in a placebo-controlled study in type 2 diabetes: results from the Diabetes Atherosclerosis Intervention Study (DAIS). Am J Kidney Dis 2005 Mar; 45(3): 485–93.

    Article  PubMed  CAS  Google Scholar 

  142. Elam MB, Lovato LC, Byington RP, et al. Hypertriglyceridemia and low HDL-C predicts fenofibrate response in the ACCORD-Lipid trial [abstract no. 19724]. 83rd Annual Scientific Sessions of the American Heart Association; 2010 Nov 13–17; Chicago (IL).

  143. Elam M, Lovato L, Ginsberg H. The ACCORD-Lipid study: implications for treatment of dyslipidemia in type 2 diabetes mellitus. Clin Lipidol 2011 Feb; 6(1): 9–20.

    Article  CAS  Google Scholar 

  144. Vakkilainen J, Steiner G, Ansquer J-C, et al. Relationships between low-density lipoprotein particle size, plasma lipoproteins, and progression of coronary artery disease: the Diabetes Atherosclerosis Intervention Study (DAIS). Circulation 2003 Apr 8; 107(13): 1733–7.

    Article  PubMed  Google Scholar 

  145. Sullivan D, Donoghoe M, Simes J, et al. Long-term fenofibrate use is associated with reduced prevalence of liver enzyme elevation in the FIELD study [abstract no. P496]. 15th International Symposium on Atherosclerosis; 2009 Jun 14–18; Boston (MA).

  146. Enger C, Gately R, Ming EE, et al. Pharmacoepidemiology safety study of fibrate and statin concomitant therapy. Am J Cardiol 2010 Dec 1; 106(11): 1594–601.

    Article  PubMed  CAS  Google Scholar 

  147. Farnier M. Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing. Vasc Health Risk Manag 2008; 4(5): 991–1000.

    PubMed  CAS  Google Scholar 

  148. Abourbih S, Filion KB, Joseph L, et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med 2009 Oct; 122(10): 962.e1–8.

    Article  PubMed  CAS  Google Scholar 

  149. Tenkanen L, Mänttäri M, Kovanen PT, et al. Gemfibrozil in the treatment of dyslipidemia: an 18-year mortality follow-up of the Helsinki Heart Study. Arch Int Med 2006 Apr 10; 166(7): 743–8.

    Article  CAS  Google Scholar 

  150. Manninen V, Tenkanen L, Koskinen P, et al. Joint effects of serum triglyceride and LDL cholesterol and HDL cholesterol concentrations on coronary heart disease risk in the Helsinki Heart Study: implications for treatment. Circulation 1992 Jan; 85(1): 37–45.

    Article  PubMed  CAS  Google Scholar 

  151. Tenenbaum A, Fisman EZ, Boyko V, et al. Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate. Arch Int Med 2006 Apr 10; 166(7): 737–41.

    Article  CAS  Google Scholar 

  152. Tenenbaum A, Motro M, Fisman EZ, et al. Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome. Arch Intern Med 2005 May 23; 165(10): 1154–60.

    Article  PubMed  CAS  Google Scholar 

  153. The BIP Study Group. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation 2000 Jul 4; 102(1): 21–7.

    Article  Google Scholar 

  154. Rubins HB, Robins SJ, Collins D, et al. Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veteran Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch Intern Med 2002 Dec 9/23; 162: 2597–604.

    Article  PubMed  CAS  Google Scholar 

  155. Robins SJ, Collins D, Wittes JT, et al. Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial. JAMA 2001 Mar 28; 285(12): 1585–91.

    Article  PubMed  CAS  Google Scholar 

  156. Simó R, Hernández C. Advances in the medical treatment of diabetic retinopathy. Diabetes Care 2009 Aug; 32(8): 1556–62.

    Article  PubMed  CAS  Google Scholar 

  157. Davis TM, Yeap BB, Davis WA, et al. Lipid-lowering therapy and peripheral sensory neuropathy in type 2 diabetes: the Fremantle Diabetes Study. Diabetologia 2008 Apr; 51(4): 562–6.

    Article  PubMed  CAS  Google Scholar 

  158. Barter P, Gotto AM, LaRosa JC, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med 2007 Sep 27; 357(13): 1301–10.

    Article  PubMed  CAS  Google Scholar 

  159. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008 Jun 12; 358(24): 2545–59.

    Article  PubMed  CAS  Google Scholar 

  160. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010 Apr 29; 362(17): 1575–85.

    Article  PubMed  CAS  Google Scholar 

  161. Tonkin AM, Chen L. Effects of combination lipid therapy in the management of patients with type 2 diabetes mellitus in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Circulation 2010 Aug 24; 122(8): 850–2.

    Article  PubMed  Google Scholar 

  162. Fruchart JC, Sacks FM, Hermans MP. Implications of the ACCORD lipid study: perspective from the Residual Risk Reduction Initiative (R3i). Curr Med Res Opin 2010 Aug; 26(8): 1793–7.

    Article  PubMed  CAS  Google Scholar 

  163. D’Emden M, Li LP, Zannino D, et al. Effect of fenofibrate on cardiovascular events and mortality in women with type 2 diabetes: results from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study [abstract no. 662-P]. 69th Annual Scientific Sessions of the American Diabetes Association; 2009 Jun 5–9; New Orleans (LA).

  164. American Diabetes Association. Standards of medical care in diabetes: 2011. Diabetes Care 2011 Jan; 34 Suppl. 1: S11–61.

    Article  CAS  Google Scholar 

  165. Davidson MH, Armani A, McKenney JM, et al. Safety considerations with fibrate therapy. Am J Cardiol 2007 Mar 19; 99(6A): 3–18C.

    Article  CAS  Google Scholar 

  166. Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol 2005 Jan 1; 95(1): 120–2.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Gillian M. Keating.

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Various sections of the manuscript reviewed by: J. Ducobu, Université de Mons-Hainaut, Mons, Belgium; M.B. Elam, Department of Pharmacology and Medicine, University of Tennessee Health Sciences Center-Memphis, Memphis, TN, USA; M. Farnier, Point Medical, Dijon, France; K.G. Parhofer, Medical Department II Grosshadern, University of Munich, Munich, Germany; P. Poirier, Université; Laval, Québec, QC, Canada; J. Saltevo, Department of Internal Medicine, Central Hospital of Middle Finland, Jyväskylä, Finland; G.F. Watts, School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.

Data Selection

Sources: Medical literature (including published and unpublished data) on ‘fenofibrate’ was identified by searching databases since 1988 (including MEDLINE, EMBASE, and inhouse AdisBase), bibliographies from published literature, clinical trial registries/databases, and websites (including those of regional regulatory agencies and the manufacturer). Additional information (including contributory unpublished data) was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE, and AdisBase search terms were ‘fenofibrate’ and (‘hyperlipidemias’ or ‘hyperlipidaemia’ or ‘dyslipidemias’ or ‘dyslipidemia’ or ‘dyslipidaemia’). Searches were last updated 31 May 2011.

Selection: Studies in patients with primary dyslipidemia, the metabolic syndrome, or type 2 diabetes mellitus who received fenofibrate. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Fenofibrate, dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, pharmacodynamics, pharmacokinetics, therapeutic use, tolerability.

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Keating, G.M. Fenofibrate. Am J Cardiovasc Drugs 11, 227–247 (2011). https://doi.org/10.2165/11207690-000000000-00000

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