Olezarsen in hypertriglyceridemia with high cardiac risk: A GRADE-assessed meta-analysis of randomized trials with trial sequential evidence

Authors

• Ahmed Emara, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
• Ameer Awashra, Department of Medicine, An-Najah National University, Nablus, West Bank, Palestine.
• Heba Aboeldahab, Clinical Research Department, El-Gomhoria General Hospital, MOHP, Alexandria, Egypt.
• Ahmed Farid Gadelmawla, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
• Hamza A. Abdul-Hafez, Department of Medicine, An-Najah National University, Nablus, West Bank, Palestine.
• Abdullah M. Alharran, Arabian Gulf University, Manama, Kingdom of Bahrain.
• Amal A. Alsubaiei, Kuwait Institute for Medical Specializations, Kuwait City, Kuwait.
• Muneera Jasim AlRumaihi, Arabian Gulf University, Manama, Kingdom of Bahrain.
• Sara Ahmed Albuhmaid, Arabian Gulf University, Manama, Kingdom of Bahrain.
• Abdalhakim Shubietah, Advocate Health - MidwestFollow

Recommended Citation

Emara A, Awashra A, Aboeldahab H, et al. Olezarsen in Hypertriglyceridemia With High Cardiac Risk: A GRADE-Assessed Meta-Analysis of Randomized Trials With Trial Sequential Evidence. Endocrinol Diabetes Metab. 2026;9(3):e70220. doi:10.1002/edm2.70220

Affiliations

Advocate Illinois Masonic Medical Center

Abstract

Background: Hypertriglyceridemia is a widely prevalent disorder of lipid metabolism that increases the risk of cardiovascular disease and pancreatitis, and it often remains difficult to control even with standard treatments. Olezarsen, an antisense oligonucleotide that targets apolipoprotein C-III (ApoC-III), offers a new and promising option for lowering triglyceride levels.

Methods: A systematic search of PubMed, Scopus, Web of Science, and Cochrane was conducted through September 2025 to identify randomized controlled trials (RCTs) comparing olezarsen with placebo in adults with hypertriglyceridemia at high cardiovascular risk. Dichotomous outcomes were analysed as risk ratios (RRs) and continuous outcomes as percentage mean differences (MDs), both with 95% confidence intervals (CIs).

Results: Four RCTs (n = 1615 patients) were included. Olezarsen significantly reduced triglycerides (MD -47.71%, 95% CI -56.78 to -38.64, p < 0.0001), non-HDL-C (MD -22.11%, 95% CI -28.48 to -15.75, p < 0.0001), ApoC-III (MD -68.93%, 95% CI -77.54 to -60.31, p < 0.0001), VLDL-C (MD -48.52%, 95% CI -57.16 to -39.87, p < 0.0001), and ApoB (MD -10.67%, 95% CI -16.83 to -4.51, p = 0.0007), while increasing HDL-C (MD 35.13%, 95% CI -27.30 to -42.96, p < 0.0001). LDL-C showed no significant change. The risks of any or serious adverse events were comparable to placebo. Olezarsen was associated with fewer acute pancreatitis events (p = 0.035) but higher rates of liver enzyme elevations ≥ 3× ULN (p = 0.046).

Conclusions: Olezarsen demonstrated consistent improvements in triglycerides and other atherogenic lipid parameters with an overall acceptable safety profile. These findings suggest that olezarsen may be a useful adjunct option for patients with persistent hypertriglyceridemia despite standard therapy. Further large-scale and long-term studies are needed to confirm its cardiovascular and safety outcomes.

Type

Article

PubMed ID

42010388