Saroglitazar Magnesium

Saroglitazar is a potent PPAR-alpha agonist (PPAR stands for Peroxisome Proliferator Activated Receptor) with moderate PPAR-gamma agonistic activity. PPARs are nuclear lipid-activated transcription factors. They regulate the expression of various genes involved in the control of lipid and lipoprotein metabolism, glucose homeostasis and inflammatory processes. The medicine showed both anti-dyslipidemic and anti-diabetic effects, mainly through activation of PPARα and PPARγ respectively. PPARα activation increases the hepatic oxidation of fatty acids (FA) and reduces the synthesis and secretion of TG. This in turn increases diversion of FA from peripheral tissues (e.g. skeletal muscle and fat tissue) to the liver, so both FA synthesis and delivery of TG to peripheral tissues fall. Saroglitazar also increases lipolysis and the elimination of TG-rich particles from plasma. It does this by activating lipoprotein lipase (LPL) and by reducing production of apolipoprotein C-III (an inhibitor of LPL activity). In line with this mechanism, plasma LDL cholesterol was also found to be reduced. PPARα activation also increases the synthesis of apolipoproteins A-I, A-II and HDL-cholesterol. Although it is mainly a PPARα agonist, it also activates PPARγ and regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport and utilization. It increases the expression of numerous PPARγ-responsive genes involved in carbohydrate and lipid metabolism, including adiponectin, adipocyte fatty-acid binding protein (aP2), LPL, fatty acid transport protein (FATP) and fatty acid translocase (CD36). Through these genes, saroglitazar decreases the post prandial rise of plasma free fatty acids, improves post-absorptive insulin-mediated suppression of hepatic glucose output, reduces the metabolic burden on liver and muscle, and promotes glucose utilization. Strong antidiabetic and insulin sensitizing effects were observed in preclinical models.