Efficacy of Olezarsen in severe hypertriglyceridemia and acute pancreatitis risk: A systematic review and meta-analysis of randomized controlled trials

Purpose Olezarsen has shown efficacy in hypertriglyceridemic and dyslipidemic populations of mixed cohorts, but its effectiveness in severe hypertriglyceridemia(SHTG) is unknown.This is systematic review and meta-analysis to evaluate the efficacy of olezarsen in SHTG and associated risk of pancreatitis. Method PubMed, Embase, and Cochrane databases were systematically searched for published trials comparing olezarsen vs. placebo in SHTG patients up to December 03, 2025. We computed mean difference (MD) and risk ratio (RR) with 95% CI for continuous and binary endpoints, respectively, using a random-effects model.Significance level was set with P-value(< 0.05) Results From 228 database records, three randomized trials involving a total of 1,127 patients were included. Of these, 748 patients (66.3%) received olezarsen. Olezarsen significantly reduced the mean percentage change from baseline of triglyceride (TG) levels (MD = -55.01%;95% CI: -61.97, -48.06; P = .00001), of apolipoprotein C-III levels (MD = -65.66%; 95% CI: -70.75, -60.57; P = .00001) compared to placebo. Significant reductions were also observed for other lipid parameters, specifically Non-high-density lipoprotein cholesterol (non-HDL-C) (MD = -23.92%;95% CI: -26.93, -20.91; P = .00001) and Remnant cholesterol(RC) (MD = -55.30%;95% CI: -62.05, -48.56; P = .00001) with reduced risk of acute pancreatitis (1.2% vs 8.7%; RR = 0.14; 95% CI: 0.07, 0.29; P = .00001) compared to placebo. No significant adverse events were observed between groups. Conclusion Olezarsen significantly reduced TG, apolipoprotein C-III, and other lipid parameters while reducing acute pancreatitis risk without increasing adverse events. These findings are suggestive that olezarsen is an effective alternative therapy for patients with SHTG.