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Review
. 2025 Aug 26.
doi: 10.1007/s10557-025-07764-4. Online ahead of print.

Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Homozygous Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Efficacy and Safety

Mohamed Nasser #  1 , Hazem E Mohammed #  2 , Mohamed E Haseeb  3 , Mohamed Khalafalla Darwish  3 , George Hanen  3   4 , Nada A Abdelaziz  3 , Anas Hussien Heiba  3 , Abdelrahman Shata  5   4 , Mohamed Salem Abdelkader  3
Affiliations
Review

Lomitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, in Homozygous Familial Hypercholesterolemia: A Systematic Review and Meta-Analysis of Efficacy and Safety

Mohamed Nasser et al. Cardiovasc Drugs Ther. .

Abstract

Purpose: Homozygous Familial Hypercholesterolemia (HoFH) is a rare and life-threatening genetic disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset atherosclerotic cardiovascular disease. Lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor, decreases LDL-C independent of LDL receptor function, providing an alternative treatment in this population. We aimed to evaluate the efficacy and safety of lomitapide in patients with HoFH through a systematic review and meta-analysis of available clinical evidence.

Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science through March 2025. Observational studies and clinical trials reporting on lipid profile changes and safety outcomes in HoFH patients receiving lomitapide were included. Outcomes were pooled using random-effects models, and heterogeneity was assessed using the I2 statistic.

Results: Eight studies comprising both adult and pediatric patients (n = 209) were included. Lomitapide significantly reduced LDL-C levels by 49.27%, total cholesterol by 46.05%, and apolipoprotein B by 51.01%. Reductions were also observed in triglycerides, VLDL-C, and non-HDL-C. HDL-C remained relatively unchanged. Adverse events were mostly gastrointestinal, with a 14% discontinuation rate. The overall quality of studies ranged from fair to good.

Conclusions: Lomitapide demonstrates substantial efficacy in reducing LDL-C and other atherogenic lipids in HoFH patients, with an acceptable safety profile. These findings support its role as an adjunctive therapy in this population, though further randomized controlled trials are warranted to validate long-term safety and effectiveness.

Keywords: HoFH; Homozygous Familial Hypercholesterolemia; Lomitapide; Meta-analysis; Microsomal triglyceride transfer protein inhibitor; Systematic review.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Conflict of interest: The authors declare that they have no competing interests. Human ethics and consent to participate statement: Our manuscript was not applied to human beings and thus requires no ethical approval.

References

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