reductase, known collectively as HMG-CoA reductase inhibitors (or "statins"), are used to lower serum cholesterol as a means of reducing the risk for cardiovascular disease. These drugs include rosuvastatin (CRESTOR), lovastatin (Mevacor), atorvastatin (Lipitor), pravastatin (Pravachol), fluvastatin (Lescol), pitavastatin (Livalo), and simvastatin (Zocor). Red yeast rice extract, one of the fungal sources from which the statins were discovered, contains several naturally occurring cholesterol-lowering molecules known as monacolins. The most active of these is monacolin K, or lovastatin (previously sold under the trade name Mevacor, and now available as generic lovastatin). Vytorin is drug that combines the use simvastatin and ezetimibe, which slows the formation of cholesterol by every cell in the body, along with ezetimibe reducing absorption of cholesterol, typically by about 53%, from the intestines. Statins, HMG-CoA reductase inhibitors, are competent in lowering cholesterol levels and reducing cardiac-related diseases. However, there have been controversies surrounding the potential of statins increasing the risk of new-onset diabetes mellitus (NOD). Experiments have demonstrated that glucose and cholesterol homeostasis are regulated by statins. The HMG-CoA reductase (HMGCR), converts HMG-CoA into mevalonic acid. Thus, when HMGCR activities are reduced, the cell associated cholesterols are also reduced. This results in the activation of SREBP-2-mediated signaling pathways. SREBP-2 activation for cholesterol homeostasis is crucial for the upregulation of low density lipoprotein (LDL) receptor (LDLR). The removal of LDL particles from blood circulation is enhanced when the number of LDLR on hepatocytes increases. Due to the removal of atherogenic lipoprotein particles, such as LDLs and intermediate density lipoproteins, HMGCR inhibitors have been proven to be efficient in reducing cardiovascular diseases from the blood circulation, which is represented by the reduction of LDL-cholesterol levels. In many studies, lipophilic statins are shown as more diabetogenic, possibly due to the fact that they can easily diffuse into cells and inhibit the production of isoprenoids which become more potent. Additionally, statins have been shown to change glucose levels as well. Hormones HMG-CoA reductase is active when blood glucose is high. The basic functions of insulin and glucagon are to maintain glucose homeostasis. Thus, in controlling blood sugar levels, they indirectly affect the activity of HMG-CoA reductase, but a decrease in activity of the enzyme is caused by AMP-activated protein kinase, which responds to an increase in AMP concentration, and also to leptin. Clinical significance Since the reaction catalysed by HMG-CoA reductase is the rate-limiting step in cholesterol synthesis, this enzyme represents