While
glycemic control remains the cornerstone of clinical management for patients with
type 2 diabetes, the importance of a more comprehensive approach that addresses the multiple metabolic abnormalities seen in this population is now widely recognized. Abnormal lipid metabolism resulting in
dyslipidemia contributes greatly to the markedly increased risks of
cardiovascular disease observed in diabetic patients and in prediabetic patients with signs of
insulin resistance. The
peroxisome proliferator-activated receptors (PPARs) play a key role in the regulation of energy homeostasis and the coordination of inflammatory responses. As such, they are interesting targets for addressing both the
glucose and
lipid abnormalities associated with
insulin resistance. The
thiazolidinediones (TZDs), which activate
PPARgamma, appear to improve
glycemic control primarily by increasing peripheral
insulin sensitivity and reducing hepatic
glucose production, thereby helping to preserve beta-cell function. They have also demonstrated modest beneficial effects on some
lipid parameters. The
fibrate drugs, which activate
PPARalpha, produce robust improvements in
dyslipidemia, decrease atherosclerotic lesions and may have an effect on cardiovascular events, but do not affect glycemia. Theoretically, a compound targeting both the alpha and gamma PPARs simultaneously might combine the benefits of TZDs and
fibrates.
Tesaglitazar is a dual-acting
PPARalpha/gamma agonist currently being investigated in phase III clinical trials as an alternative treatment for
insulin resistance and the characteristic dyslypidemia of
type 2 diabetes. This article reviews the available data on the clinical efficacy and safety of
tesaglitazar in patients with
type 2 diabetes and in individuals without diabetes but with
insulin resistance.