Treatment of severe hypertriglyceridemia: a new era dawns

Abstract Context Hypertriglyceridemia (HTG) is a well-established independent cardiovascular risk factor. Severe (triglycerides [TGs] > 500 mg/dL) or extreme HTG (> 1000 mg/dL) that persist despite the correction of secondary causes are also associated with a markedly increased risk of recurrent acute pancreatitis and represent a substantial unmet medical need. Several novel therapies are progressively emerging and being incorporated into the treatment landscape for the management of severe HTG (sHTG) and associated risks. Evidence acquisition Naturally occurring loss-of-function variants in genes involved in TG metabolism have been identified; carriers of these variants tend to exhibit a favorable lipid profile and reduced cardiovascular risk. Therapeutic strategies have been developed to inhibit these genes or their corresponding proteins through diverse mechanisms of action. In addition, several other proteins and hormones influencing TG metabolism have been identified in the last decade and have emerged as promising targets for sHTG treatment. Evidence synthesis This review summarizes novel therapeutic targets, mechanisms of action, and the ongoing clinical development of emerging treatments aimed at improving the management of TG-rich lipoproteins, reducing TG levels and mitigating associated risks. Conclusion sHTG remains an important unmet medical need. Considerable research efforts are currently focused on the development of innovative, effective, and safe therapeutic interventions aimed at reducing the risks associated with sHTG. At present, the use of most of these emerging therapies remains limited to selected patient populations, while broader indications continue to be investigated.