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Residual vascular risk in diabetes – will the SPPARM alpha concept hold the key?

Despite advances in best treatment targeting blood pressure, low-density lipoprotein (LDL) cholesterol and glycaemia (for microvascular disease), individuals with type 2 diabetes continue to experience cardiovascular events. Therapeutic strategies aimed at additional targets are clearly needed. One approach is to target the nuclear peroxisome proliferator-activated receptor alpha (PPARα), which exerts both positive and negative control on genes involved in fatty acid oxidation, lipoprotein metabolism and inflammation. In particular, effects including increased HDL production, very-low-density lipoprotein (VLDL) clearance and LDL particle size, as well as reduction in VLDL production and LDL particle concentration, imply a key role for PPARα agonism in managing atherogenic dyslipidaemia (high plasma triglycerides, low HDL cholesterol, small-dense LDL particles, and elevated apolipoprotein B and C-III), a key lipid trait associated with type 2 diabetes. Current PPARα agonists are limited by low potency and side effects. Clinical studies with these agents have also failed to show definitive benefit in reducing cardiovascular events, against a background of best evidence-based treatment including statin. New approaches are needed. This comment from internationally renowned leaders in cardiovascular disease prevention makes the case for the SPPARMα (Selective Peroxisome Proliferator-Activated Receptor Alpha Modulator) concept. This new class of pharmacological agents aims to maximize favourable effects associated with PPARα activation while simultaneously limiting the propensity for unwanted effects. This concept is being tested in the cardiovascular outcomes study PROMINENT. SPPARM alpha may offer the key to addressing residual cardiovascular risk.
Residual vascular risk in diabetes – will the SPPARM alpha concept hold the key?

Fruchart J-C, Santos RD, Yamashita S, Libby P