Microsomal transfer protein inhibition in humansCuchel, Marina; Rader, Daniel J.Current Opinion in Lipidology: June 2013 - Volume 24 - Issue 3 - p 246–250 doi: 10.1097/MOL.0b013e32836139df LIPID METABOLISM: Edited by Ernst J. Schaefer Abstract Author Information Purpose of review Microsomal triglyceride transfer protein (MTP) is a key protein in the secretion of apolipoprotein B-containing lipoproteins. Its pharmacological inhibition is associated with a decrease in LDL cholesterol (LDL-C) and triglycerides. However, the clinical use of MTP inhibitors has been uncertain because of the gastrointestinal adverse events and the increase in liver fat content observed during their administration. Recent findings Lomitapide, a systemic MTP inhibitor, significantly reduces LDL-C in homozygous familial hypercholesterolemia (hoFH) when administered concurrently with other lipid-lowering therapies, including apheresis. Its lipid-lowering effect is additive to that of existing drugs. In the presence of an up-titration regiment and low-fat diet, lomitapide is generally well tolerated and liver fat accumulation stabilizes after the initial increase. Elevation of alanine aminotranferase levels greater than 3 times the upper limit of normal can be managed successfully with temporary dose reduction. Drug–drug interaction studies show that concomitant treatment of lomitapide with other lipid-lowering drugs is generally safe. Based on these findings, lomitapide was recently approved for the treatment of hoFH as add-on therapy. Summary MTP inhibition is a valuable therapeutic approach for hoFH. Long-term safety consequences of liver fat accumulation will need to be assessed. Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA Correspondence to Marina Cuchel, MD, PhD, Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, Philadelphia, PA 19104, USA. Tel: +1 215 746 2834; e-mail: firstname.lastname@example.org © 2013 Lippincott Williams & Wilkins, Inc.