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Treatment of severe hypertriglyceridemia: a new era dawns
Miriam Larouche1, Daniel Gaudet1
1Department of Medicine, Université de Montréal and ECOGENE-21, Chicoutimi, Canada G7H 7K9.
Insights
Severe hypertriglyceridemia (HTG) poses significant cardiovascular and pancreatitis risks. Emerging therapies targeting triglyceride metabolism offer new hope for managing this unmet medical need.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Pharmacology
Background:
- Hypertriglyceridemia (HTG) is a key cardiovascular risk factor.
- Severe HTG increases risks of pancreatitis and cardiovascular events, representing an unmet need.
- Novel therapies are emerging for severe HTG management.
Purpose of the Study:
- To review novel therapeutic targets and mechanisms for severe HTG.
- To summarize the clinical development of emerging treatments for triglyceride-rich lipoproteins.
- To discuss risk mitigation strategies for severe HTG.
Main Methods:
- Review of naturally occurring loss-of-function variants in genes related to triglyceride metabolism.
- Identification of novel proteins and hormones influencing triglyceride metabolism as therapeutic targets.
- Analysis of ongoing clinical development for emerging severe HTG treatments.
Main Results:
- Emerging therapies target key pathways in triglyceride metabolism.
- Clinical development focuses on reducing triglyceride levels and associated risks.
- Novel mechanisms of action are being explored for severe HTG.
Conclusions:
- Severe HTG remains a significant unmet medical need.
- Innovative therapies are under development to improve safety and efficacy.
- Current emerging therapies have limited indications, with broader use under investigation.
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.
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