INTRODUCTION: The prevalence of hypertriglyceridemia (HTG) is increasing. 
Elevated triglyceride (TG) levels are associated with an increased 
cardiovascular disease (CVD) risk. Moreover, severe HTG results in an elevated 
risk of pancreatitis, especially in severe HTG with an up to 350-fold increased 
risk. Both problems emphasize the clinical need for effective TG lowering.
AREAS COVERED: The purpose of this review is to discuss the currently available 
therapies and to elaborate the most promising novel therapeutics for TG 
lowering.
EXPERT OPINION: Conventional lipid lowering strategies do not efficiently lower 
plasma TG levels, leaving a residual CVD and pancreatitis risk. Both 
apolipoprotein C-III (apoC-III) and angiopoietin-like 3 (ANGPTL3) are important 
regulators in TG-rich lipoprotein (TRL) metabolism. Several novel agents 
targeting these linchpins have ended phase II/III trials. Volanesorsen targeting 
apoC-III has shown reductions in plasma TG levels up to 90%. Multiple ANGPLT3 
inhibitors (evinacumab, IONIS-ANGPTL3-LRx, ARO-ANG3) effectuate TG reductions up 
to 70% with concomitant potent reduction in all other apoB containing 
lipoprotein fractions. We expect these therapeutics to become players in the 
treatment for (especially) severe HTG in the near future.