Current and Emerging Pharmacological Therapies for Hypertriglyceridemia

Area of Science:

• Biochemistry and Molecular Biology
• Cardiovascular Medicine
• Metabolic Disorders

Background:

• Severe hypertriglyceridemia significantly elevates atherosclerotic cardiovascular disease risk and predisposes individuals to acute pancreatitis.
• Existing treatments and lifestyle changes are often insufficient for patients with refractory hypertriglyceridemia.

Purpose of the Study:

• To review triglyceride metabolism and the role of remnant lipoproteins in atherogenesis.
• To provide an overview of emerging triglyceride-lowering therapies and their clinical evidence.

Main Methods:

• Review of molecular mechanisms regulating triglyceride metabolism, including lipoprotein lipase (LPL), apolipoprotein C-III (ApoC-III), and angiopoietin-like proteins (ANGPTLs).
• Analysis of clinical trial data for novel therapeutic agents targeting these regulatory pathways.

Main Results:

• Emerging therapies, including antisense oligonucleotides (ASOs), small interfering RNA (siRNA), ANGPTL3 inhibitors, and FGF-21 analogs, demonstrate substantial triglyceride reduction (up to 80%).
• Preliminary data suggest these therapies may decrease acute pancreatitis incidence and improve cardiometabolic risk, pending further trials.

Conclusions:

• Targeting key proteins in triglyceride metabolism offers a promising therapeutic strategy for severe hypertriglyceridemia.
• Novel agents are rapidly evolving the treatment landscape, necessitating individualized plans, lifestyle support, and safety monitoring.