Mustafa, Muhammad Saqlain

Background: Hypertriglyceridemia, a common lipid disorder linked to increased risks of cardiovascular diseases and metabolic syndrome, remains a global health challenge. Traditional treatments, though widely used, often have limited efficacy and adverse effects. Olezarsen, a novel antisense oligonucleotide, targets apolipoprotein C-III and shows promise in significantly reducing triglyceride levels. Aim: To conduct a meta-analysis comparing Olezarsen with placebo in patients with hypertriglyceridemia. Methods: We performed an extensive literature search of PubMed, EMBASE, and Cochrane Library databases up to May 2024 to identify studies comparing Olezarsen and placebo in patients with hypertriglyceridemia, irrespective of comorbid cardiovascular disease. Effect estimates were pooled using a random-effects model and reported as risk ratios (RR) for dichotomous outcomes and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs) for each. Results: Three randomized controlled trials (RCTs) with a total of 334 participants were included. Olezarsen significantly reduced triglyceride levels at 6 months (SMD: -1.69; 95% CI -2.22 to -1.17; P < 0.00001; Figure ) and 12 months (SMD: -1.64; 95% CI -2.22 to -1.07; P < 0.00001; Figure ). VLDL levels also decreased at 6 months (SMD: -1.95; 95% CI -2.38 to -1.51; P < 0.00001) and 12 months (SMD: -0.83; 95% CI -1.13 to -0.53; P < 0.00001). Lipid profile improvements included reductions in total cholesterol, non-HDL cholesterol, and apoB levels, with increases in HDL cholesterol and apoA-1. Adverse events were comparable between Olezarsen and placebo, although serious adverse events were significantly higher in the Olezarsen group (RR: 2.55; 95% CI 1.17 to 5.58; p = 0.02). Conclusion: Olezarsen demonstrates significant efficacy in reducing triglyceride and VLDL levels while improving overall lipid profiles in hypertriglyceridemia patients. Despite higher rates of serious adverse events, its overall safety profile remains acceptable.

Introduction: Non-alcoholic fatty liver disease (NAFLD), spanning from non-alcoholic steatohepatitis (NASH) to liver fibrosis, poses a global health challenge amid rising obesity and metabolic syndrome rates. Effective pharmacological treatments for NASH and liver fibrosis are limited. Objective: This study systematically reviews and meta-analyzes the safety and efficacy of resmetirom, a selective thyroid hormone receptor-β agonist, in NASH and liver fibrosis treatment. By analyzing data from clinical trials, we aim to offer evidence-based recommendations for resmetirom’s use in managing these conditions and identify avenues for future research. Methods: Electronic databases (PubMed, Scopus, Science Direct, Google Scholar, ClinicalTrials.gov, and Cochrane CENTRAL) were systematically searched, supplemented by manual screening of relevant sources. Only English-language randomized controlled trials were included. Data extraction, risk of bias assessment, pooled analyses, and meta-regression were performed. Results: Three randomized controlled trials involving 2231 participants were analyzed. Resmetirom demonstrated significant reductions in hepatic fat fraction [standardized mean difference (SMD) −4.61, 95% CI −6.77 to −2.44, P < 0.0001], NASH resolution without worsening fibrosis [risk ratio (RR) 2.51, 95% CI 1.74–3.64, P = 0.00001), and liver fibrosis improvement (RR 2.31, 95% CI 1.20–4.44, P = 0.01). Secondary outcomes showed significant improvements in lipid profiles, liver enzymes, and NASH biomarkers with resmetirom treatment. Meta-regression revealed associations between covariates and primary outcomes. Conclusion: Resmetirom exhibits promising efficacy in reducing hepatic fat, improving NASH resolution, and ameliorating liver fibrosis with a favorable safety profile. Further research is warranted to validate findings and optimize therapeutic strategies for NASH and liver fibrosis management.