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Efficacy and Safety of Apolipoprotein C-III Inhibitors in Hypertriglyceridemia: A Network Meta-Analysis of Randomised

Mohammed A Elbahloul1, Aliaa Gamal2, Odai Maihoub3

  • 1Faculty of Medicine, Kafr El-Shaikh University, Kafr El Shaikh, Egypt.

Diabetes, Obesity & Metabolism
|April 1, 2026
PubMed

Insights

Apolipoprotein C-III (ApoC-III) inhibitors effectively lower triglyceride levels and reduce pancreatitis risk in hypertriglyceridemia patients. These agents show promise for improving lipid profiles and cardiovascular health without increasing serious adverse events.

Area of Science:

  • Cardiovascular Medicine
  • Pharmacology
  • Biochemistry

Background:

  • Hypertriglyceridemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD).
  • Apolipoprotein C-III (ApoC-III) plays a key role in triglyceride metabolism.
  • Targeting ApoC-III offers a potential therapeutic strategy for managing hypertriglyceridemia.

Purpose of the Study:

  • To evaluate the efficacy and safety of apolipoprotein C-III (ApoC-III) inhibitors in patients with hypertriglyceridemia.
  • To compare the effects of different ApoC-III inhibitors on lipid parameters and pancreatitis risk.
  • To assess the overall impact of ApoC-III inhibition on cardiovascular disease risk factors.

Main Methods:

  • Systematic search of electronic databases for randomized controlled trials (RCTs).
  • Frequentist network meta-analysis comparing ApoC-III inhibitors (Volanesorsen, Olezarsen, Plozasiran) with placebo.
  • Analysis of continuous outcomes (mean differences) and dichotomous outcomes (risk ratios) with 95% confidence intervals.

Main Results:

  • 15 RCTs with 3934 patients were included.
  • Most ApoC-III inhibitors significantly reduced triglycerides (TG), with Olezarsen 80 mg Q4W showing the highest efficacy (MD: -63.26).
  • ApoC-III inhibitors significantly reduced pancreatitis incidence (HR: 0.16) and did not increase serious adverse events.

Conclusions:

  • ApoC-III inhibitors are effective in improving triglyceride levels and other lipid parameters.
  • These inhibitors substantially reduce the risk of acute pancreatitis.
  • Further research is warranted to investigate the long-term cardiovascular outcomes associated with ApoC-III inhibitors.
Abstract

Keywords:
OlezarsenPlozasiranVolanesorsenapolipoprotein C‐III inhibitorshypertriglyceridemia

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