Fibrate therapy in patients with metabolic syndrome and diabetes mellitus

Patients with metabolic syndrome and type 2 diabetes mellitus are usually in moderately high-risk, high-risk, or very high-risk cardiovascular categories and present major therapeutic challenges. The dyslipidemia in such patients is typically a disorder of the triglyceride/high-density lipoprotein axis (TG/HDL axis) characterized by an excess of triglyceride-rich lipoproteins and a reduction of HDL. Very often, lifestyle therapy and statin monotherapy fail to achieve guideline goals, necessitating combination therapies. Fibric acids (or fibrates), are agonists of peroxisome proliferator-activated receptor α, which have amassed significant lipid-surrogate and clinical outcome trial data, especially in insulin-resistant patients, typical of those with metabolic syndrome or type 2 diabetes mellitus. Current guidelines advocate fibrate use as an add-on to statin therapy when TG/HDL abnormalities exist in such patients. In this paper, we review pertinent and recent trial data, mechanisms of action, and the safety of fibrate therapy.