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Diabetes and Vascular Disease Research
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The role of fenofibrate in clinical practice

Alberto Zambon

Centre for Atherosclerosis Prevention and Treatment, Department of Medicine, Policlinico Universitario, Via Giustiniani 2, 35128 Padua, Italy.

Kenneth Cusi

Department of Medicine, Diabetes Division, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, Texas 78229-3900, US.

Clinical guidelines highlight the importance of dyslipidaemia management for reducing the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome. While statins represent the main focus of therapy, there is increasing evidence that the addition of a fibrate such as fenofibrate provides further reduction in risk. Fenofibrate also offers a number of benefits beyond lipid modification; these are mediated by peroxisome proliferator-activated receptor-alpha (PPAR{alpha}) activation and appear to be independent of effects of glucose and lipid metabolism. Furthermore, as shown by the Fenofibrate Intervention for Event Lowering in Diabetes (FIELD) study, fenofibrate treatment has promising effects in preventing progression of diabetes-related microvascular complications.

PPAR{alpha} is critical to lipid metabolism in the liver. Recent findings which showed that pioglitazone, a PPAR{gamma} agonist with weak PPAR{alpha} activity, improved fatty liver disease in patients with non-alcoholic steatohepatitis (NASH) and metabolic syndrome or type 2 diabetes have prompted interest in whether more potent PPAR{alpha} agonists, such as fenofibrate, may have a role in the management of non-alcoholic fatty liver disease (NAFLD). The combination of fenofibrate and a statin is well tolerated, with no apparent increase in the risk of myopathy, unlike gemfibrozil-statin combination therapy.

In overview, the available evidence indicates that the combination of fenofibrate with a statin is a useful approach for optimising reduction in the risk of cardiovascular disease in patients with type 2 diabetes and metabolic syndrome, as well as delaying the progression of diabetes-related microvascular complications. Data are awaited from the ongoing Action to Control Cardiovascular Risk in Diabetes (ACCORD) study to evaluate the outcome benefits of this approach.

Key Words: cardiovascular disease • combination therapy • dyslipidaemia • fenofibrate • metabolic syndrome • microvascular disease • type 2 diabetes

Diabetes and Vascular Disease Research, Vol. 4, No. 3 Suppl, S15-S20 (2007)
DOI: 10.3132/dvdr.2007.053
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