Related Experiment Video
Updated: Mar 6, 2026
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Efficacy and Safety of Lomitapide in Hypercholesterolemia
Xin Liu1,2, Peng Men3, Yuhui Wang2
1Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
Lomitapide effectively lowers LDL-C in hypercholesterolemia patients, including those with homozygous familial hypercholesterolemia (HoFH). However, it may cause gastrointestinal issues and impact HDL-C levels.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Metabolic Disorders
Background:
- Hypercholesterolemia, particularly homozygous familial hypercholesterolemia (HoFH), often fails to reach target low-density lipoprotein cholesterol (LDL-C) levels with statin therapy.
- Novel therapeutic strategies are needed to reduce proatherogenic lipoprotein cholesterol levels.
- Lomitapide, a microsomal triglyceride transport protein (MTP) inhibitor, is an approved orphan drug for HoFH treatment.
Purpose of the Study:
- To systematically evaluate the efficacy and safety of lomitapide for managing hypercholesterolemia.
- To provide clinical guidance on the use of lomitapide.
Main Methods:
- Systematic literature search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for studies published before October 31, 2016.
- Inclusion of studies involving lomitapide-treated patients, with or without concurrent lipid-lowering therapy.
- Quality assessment and data extraction by two independent reviewers.
Main Results:
- Lomitapide significantly reduced LDL-C, total cholesterol, apolipoprotein B, and triglycerides in HoFH patients, with or without other therapies.
- Favorable effects on LDL-C and triglycerides were also observed in non-HoFH patients with moderate hypercholesterolemia and hypertriglyceridemia.
- Common adverse events included gastrointestinal disorders, elevated liver transaminases, and hepatic fat accumulation, with long-term use potentially increasing the risk of steatohepatitis and fibrosis. A reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1) was noted in both HoFH and non-HoFH patients.
Conclusions:
- Lomitapide demonstrates efficacy in improving key lipid parameters, excluding HDL-C and ApoA-1, in patients with HoFH and other forms of hypercholesterolemia.
- Gastrointestinal disturbances are the most frequent adverse events associated with lomitapide treatment.
- The clinical benefits of lomitapide require careful consideration against its potential long-term adverse effects, particularly hepatic complications.
Background:
Despite extensive use of statins, patients with hypercholesterolemia, especially homozygous familial hypercholesterolemia (HoFH), do not achieve recommended targets of low-density lipoprotein cholesterol (LDL-C). There is an urgent need for novel options that could reduce proatherogenic lipoprotein cholesterol levels. Lomitapide, a microsomal triglyceride transport protein (MTP) inhibitor, was approved three years ago as an orphan drug for the treatment of patients with HoFH.
Objective:
Our aim was to systematically evaluate the efficacy and safety of lomitapide and to provide guidance for clinicians.
Methods:
We searched the PubMed, Embase, and Cochrane library databases and ClinicalTrials.gov to identify valid studies published before 31 October 2016 that included lomitapide-treated patients who did or did not undergo lipid-lowering therapy. We assessed the quality of different studies. Data were extracted and evaluated for quality by two reviewers.
Results:
Studies reporting lomitapide therapy included one randomized controlled trial, three single-arm studies, and five case reports. In patients with HoFH, lomitapide reduced levels of LDL-C, total cholesterol, apolipoprotein B, and triglycerides with or without other lipid-lowering therapy, including apheresis. In non-HoFH patients with moderate hypercholesterolemia and hypertriglyceridemia, lomitapide also showed favorable effects on changes in LDL-C and triglycerides. However, both HoFH and non-HoFH patients experienced a reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-1 (ApoA-1). The most common adverse event was gastrointestinal disorder, and others included liver transaminase elevation and hepatic fat accumulation. Long-term use of lomitapide was associated with an increased risk of progressing to steatohepatitis and fibrosis.
Conclusions:
Lomitapide improved most lipid parameters but not HDL-C or ApoA-1 in patients with HoFH and in non-HoFH patients, and gastrointestinal disorders were the most common adverse event. The possible benefits of lomitapide should be further evaluated and viewed against its possible long-term side effects.
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...
01:26Atherosclerosis III: Management
01:24Lipid Absorption
These breakdown products bind with bile salts and lecithin to form micelles, which quickly pass between microvilli to come in close contact with the apical...
01:25Lipid Catabolism
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test