Inhibitors of apolipoprotein C3, triglyceride levels, and risk of pancreatitis: a systematic review and meta-analysis

Rev Endocr Metab Disord. 2024 Oct;25(5):817-825. doi: 10.1007/s11154-024-09893-x. Epub 2024 Jul 13.

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, I2 82%) and lowered apoC3 values (MD -76; 95% CI -80.1 to -71.8, I2 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, I2 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.

Keywords: Acute pancreatitis; Apolipoprotein C3; Apolipoprotein C3 inhibitors; Triglycerides.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Apolipoprotein C-III* / antagonists & inhibitors
  • Apolipoprotein C-III* / blood
  • Humans
  • Hypertriglyceridemia* / blood
  • Hypertriglyceridemia* / complications
  • Hypertriglyceridemia* / drug therapy
  • Hypertriglyceridemia* / metabolism
  • Pancreatitis* / epidemiology
  • Pancreatitis* / metabolism
  • Pancreatitis* / prevention & control
  • Randomized Controlled Trials as Topic
  • Triglycerides* / blood
  • Triglycerides* / metabolism

Substances

  • APOC3 protein, human
  • Apolipoprotein C-III
  • Triglycerides