Peroxisome proliferator–activated receptors (PPARs) are nuclear cell transcription factors with isoform agonists that exhibit clinical benefit. The PPAR-γ agonists increase insulin sensitivity, explaining the antidiabetic action of the thiazolidinediones rosiglitazone and pioglitazone. PPAR-α agonists, including the fibrates, increase fatty acid oxidation, leading to a decrease in plasma triglycerides and a modest increase in high-density lipoprotein cholesterol. Muraglitazar is the first dual-PPAR agonist to be considered for general marketing both as monotherapy and combined therapy by the US Food and Drug Administration (FDA). Given the emerging epidemic of type 2 diabetes, it is easy to understand the enthusiasm for this new class of drugs. Tight glycemic control reduces diabetic microvascular complications, although both old1 and new2 studies have failed to convincingly show decreased macrovascular complications of stroke, cardiac disease, and peripheral vascular disease.
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