Novel triglyceride-lowering therapies to reduce the risk of acute pancreatitis in hypertriglyceridaemia: a protocol for systematic review and meta-analysis

INTRODUCTION: Hypertriglyceridaemia is a major risk factor and rising aetiology for acute pancreatitis (AP), a condition associated with significant morbidity and mortality. Novel triglyceride-lowering therapies targeting key regulators of lipoprotein metabolism, specifically apolipoprotein C-III (APOC3), angiopoietin-like 3 protein (ANGPTL3) and angiopoietin-like 4 protein (ANGPTL4), have shown promise in reducing triglyceride levels. This study aims to evaluate the efficacy and safety of APOC3, ANGPTL3 and ANGPTL4 inhibitors for reducing the episodes of AP in patients with hypertriglyceridaemia. METHODS AND ANALYSIS: A systematic search of PubMed (National Library of Medicine), Web of Science (Clarivate), Embase (Ovid) and the Cochrane Library (Wiley) will be conducted to identify randomised controlled trials published from inception to May 2026. Eligible studies will include adults with hypertriglyceridaemia (fasting triglyceride level ≥500 mg/dL (5.6 mmol/L)), comparing APOC3, ANGPTL3 or ANGPTL4 inhibitors against placebo. The primary outcome will be the incidence of AP. Secondary outcomes include the per cent change in lipid parameters (triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol) and safety profiles. Two reviewers will independently conduct study selection, data extraction and risk of bias assessment. Meta-analysis will be performed using R software, with effects expressed as risk ratio for dichotomous outcomes and mean differences for continuous outcomes. Heterogeneity, subgroup analyses, sensitivity analyses and publication bias will be assessed. The certainty of evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. ETHICS AND DISSEMINATION: Ethical review is not required as this study involves no human participants and relies on previously published data. The findings will be disseminated through peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD420251174198.