HDL biology
Review names CETP inhibitors among four novel drug classes targeting low HDL cholesterol (Expert Opin Investig Drugs 2001)
Original title: Novel agents for managing dyslipidaemia
This review argues that while statins effectively lower LDL-cholesterol and CHD risk, novel agent development is now focused on patients with low HDL-cholesterol, usually accompanying hypertriglyceridemia and linked to the growing prevalence of insulin resistance, obesity, and diabetes. It names four classes of agents with potent HDL-raising capacity in development: CETP inhibitors, retinoid X receptor selective agonists, specific PPAR agonists, and oestrogen-like compounds. It also covers a separate line of development targeting both cholesterol and triglycerides, including partial microsomal triglyceride transfer protein inhibitors, squalene synthase inhibitors, and AMP kinase agonists, concluding future therapy should correct the full lipid profile rather than LDL-cholesterol alone.
Original abstract
An elevated low-density lipoprotein (LDL) cholesterol level is a strong predictor of coronary heart disease (CHD) risk. Over the past seven years, equally strong evidence has accumulated that lowering LDL cholesterol with HMG-CoA reductase inhibitors or statins reduces CHD risk and there is now widespread use of these agents for the primary and secondary prevention of CHD. Treatment issues remain regarding the appropriate degree of LDL cholesterol reduction and whether, in people with very high levels, it would be preferable to achieve the LDL cholesterol goal with a powerful statin alone or combined with an agent that lowers LDL cholesterol by a different mechanism. The main focus in the development of novel agents is the patient with low high-density lipoprotein (HDL) cholesterol, usually associated with hypertriglyceridaemia. Already prevalent as a risk factor for CHD, this abnormality has been linked with insulin resistance, which is likely to increase greatly over the next decade, along with increasing obesity and diabetes. Agents that have potent HDL cholesterol raising capacity include cholesteryl ester transfer protein (CETP) inhibitors, retinoid X receptor (RXR) selective agonists, specific peroxisome proliferator-activated receptor (PPAR) agonists and oestrogen-like compounds. Another area of development involves agents that will lower both cholesterol and triglyceride levels, such as partial inhibitors of microsomal triglyceride transfer protein (MTP) and perhaps squalene synthase inhibitors and agonists of AMP kinase. Future emphasis will be on correcting all lipid abnormalities for the prevention of CHD, not just lowering LDL cholesterol.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.