Medicinal Chemistry

Diabetic Dyslipidemia - Role of Saroglitazar

Abstract

Anirban Majumder and Sanjay Chatterjee

‘Diabetic dyslipidemia’ (combination of raised triglyceride levels, raised small-dense Low-density lipoprotein particles and low high-density lipoprotein cholesterol levels) is the most prominent risk factor of atherosclerosis and cardiovascular disease. Despite statin therapy and LDL-lowering, a high residual risk of cardiovascular events persists. High triglyceride levels and low high-density lipoprotein cholesterol levels singly and collectively increase the risk of cardiovascular events in type 2 diabetes mellitus and guidelines recommend modifying these secondary therapeutic targets to provide additional vascular protection.Addition of a fibrate or niacinareoptions for combination with a statin to reduce atherogenic dyslipidemia and are clearly effective at raising high-density lipoprotein cholesterol levels and lowering triglycerides.Addition of high dose omega-3 fatty acids (2-3 gm/day) with a statin are also effective in lowering triglyceride, but their effects on cardiovascular events remain uncertain and are complicated with safety issues. Saroglitazar is a novel dual Peroxisome Proliferator-Activated Receptors-α/γ agonist and the first glitazar approved in the world for the treatment of diabetic dyslipidemia by Drug Controller General of India in June 2013. Saroglitazar (2 mg and 4 mg) therapy has shown significant (45%) reduction in triglycerides, significant reduction of other atherogenic lipids (Low-density lipoprotein, very-low density lipoprotein, total cholesterol and apolipoprotein-B) and significant improvement of glycemic status, with relatively free from side effects. It has emerged with a hope to further reduce the incidence of cardiovascular disease among statin treated diabetic subjects. However, the trial populations were small and toxicity data may emerge with increasing use of this drug. Moreover, in absence of outcome studies and large multi-center longitudinal follow up data, the clinical cardiovascular efficacy is uncertain till date.