Inhibitors of apolipoprotein C3, triglyceride levels, and risk of pancreatitis: a systematic review and meta-analysis
Abstract
In recent years, novel apoC3 inhibitor therapies for the treatment of hypertriglyceridemia have been developed and assessed through phase II and III clinical trials. The objective of this study was to perform an updated meta-analysis on the impact of new apoC3 inhibitor drugs on triglyceride and apoC3 levels, as well as on the incidence of pancreatitis. We conducted a meta-analysis of randomized, placebo-controlled studies assessing the effects of apoC3 inhibitors therapy (antisense oligonucleotides and small interfering RNA) on triglyceride levels, apoC3 levels, and the occurrence of acute pancreatitis. This meta-analysis was performed according to PRISMA guidelines. The random-effects model was performed. Nine randomized clinical trials (n = 717 patients) were considered eligible for this systematic review. ApoC3 inhibitor drugs were consistently associated with decreased triglyceride levels (MD -57.0%; 95% CI -61.9 to -52.1, I 2 82%) and lowered apoC3 values (MD -76; 95% CI -80.1 to -71.8, I 2 77%) when compared to placebo. Furthermore, the use of apoC3 inhibitor drugs demonstrated a reduction in the risk of acute pancreatitis (OR 0.11; 95% CI 0.04 to 0.27, I 2 0%). The present updated meta-analysis of randomized clinical trials demonstrated that the utilization of apoC3 inhibitors in patients with hypertriglyceridemia correlated with reduced apoC3 and triglyceride levels, along with a decreased risk of acute pancreatitis compared to the placebo.
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GalNAc conjugation results in more efficient liver targeting and improved potency and safety of siRNA.
“GalNAc conjugation enables selective uptake of siRNA by hepatocytes through the asialoglycoprotein receptor, resulting in more efficient liver targeting and improved potency and safety (Katzmann et al., 2020; Gao et al., 2023; Masson et al., 2024; Ward et al., 2022).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Masson et al., 2024
GalNAc conjugation enables selective uptake of siRNA by hepatocytes through the asialoglycoprotein receptor.
“GalNAc conjugation enables selective uptake of siRNA by hepatocytes through the asialoglycoprotein receptor, resulting in more efficient liver targeting and improved potency and safety (Katzmann et al., 2020; Gao et al., 2023; Masson et al., 2024; Ward et al., 2022).”
From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Masson et al., 2024
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- Authors
- Masson, W., Lobo, M., Nogueira, J. P., Corral, P., Barbagelata, L., & Siniawski, D.
- Affiliations
- Hospital Italiano de Buenos Aires (AR)
- Universidad Internacional de las Américas (CR)
- Universidad Fraternidad de Agrupaciones Santo Tomás de Aquino (AR)
- Corresponding author
- Masson, Walter
- Venue
- Reviews in Endocrine and Metabolic Disorders
- Published
- 2024-07-13
- Volume
- 25
- Issue
- 5
- Pages
- 817-825
- ISSN
- 1389-9155 (ISSN-L)
- 1573-2606
- OpenAlex
- W4400610765
- Cited by
- 12
- References
- 37
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 2
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Reviews in Endocrine and Metabolic Disorders (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- acute pancreatitis, hypertriglyceridemia, triglyceride levels, antisense oligonucleotides, siRNA, apolipoprotein C-III, drug safety
- MeSH terms
- Humans, Pancreatitis, Triglycerides, Hypertriglyceridemia, Randomized Controlled Trials as Topic, Apolipoprotein C-III
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