Efficacy and Safety of Olezarsen in Hypertriglyceridemia: An Updated Meta‐Analysis of Randomised Controlled Trials

AIMS: Hypertriglyceridemia is a common lipid disorder linked to residual cardiovascular risk and acute pancreatitis despite standard therapy. Olezarsen, an antisense oligonucleotide targeting apolipoprotein C-III (ApoC-III), offers a novel triglyceride-lowering strategy. We performed an updated meta-analysis to evaluate its efficacy and safety. METHODS AND MATERIALS: We performed a meta-analysis of randomised controlled trials (RCTs) identified through PubMed, Cochrane, Scopus and Web of Science up to December 2025. Random-effects models were used to pool mean percentage changes (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs). PROSPERO ID: CRD420261279110. RESULTS: Six RCTs with 2676 participants were analysed. Olezarsen significantly reduced triglycerides at 50 mg (MD -46.61%, 95% CI -49.59 to -43.64) and 80 mg (MD -54.37%, 95% CI -61.26 to -47.48), both p < 0.0001. ApoC-III was markedly reduced (50 mg: MD -63.51%, 95% CI -74.18 to -52.84; 80 mg: MD -66.88%, 95% CI -77.91 to -55.85; both p < 0.0001). Non-HDL-C also decreased significantly (50 mg: MD -21.41%, 95% CI -25.12 to -17.70; p < 0.0001; 80 mg: MD -25.28%, 95% CI -33.99 to -16.58; p = 0.001). LDL-C increased modestly at 50 mg (MD 17.58%, 95% CI 0.24 to 34.93; p = 0.047). Olezarsen reduced acute pancreatitis risk (50 mg: RR 0.16, 95% CI 0.05-0.48; p = 0.001; 80 mg: RR 0.33, 95% CI 0.14-0.76; p = 0.009). Overall adverse events were comparable to placebo, while ALT/AST ≥ 3 × ULN increased with 80 mg (RR 2.56, 95% CI 1.20-5.44; p = 0.01). CONCLUSIONS: Olezarsen provides substantial triglyceride reduction with favourable effects on atherogenic lipoproteins and a tolerable short-term safety profile. Longer-term trials are needed to confirm cardiovascular outcomes and safety.