Are the lipid-lowering effects of incretin-based therapies relevant for cardiovascular benefit?

Curr Opin Lipidol. 2024 Dec 1;35(6):259-267. doi: 10.1097/MOL.0000000000000949. Epub 2024 Jul 29.

Abstract

Purpose of review: This review examines the impact of glucagon-like peptide 1 receptor agonists (GLP-1RAs) on lipid profiles in individuals with type 2 diabetes mellitus and/or obesity, crucial for optimizing cardiovascular risk management.

Recent findings: GLP-1RAs affect lipid levels by reducing intestinal apolipoprotein B48 production and mesenteric lymph flow, while increasing catabolism of apolipoprotein B100. It remains unknown whether these effects are direct or indirect, but the improvements in lipid levels are strongly correlated to the drug-induced weight loss. Clinical trials demonstrate improvements in lipid profiles, with different effects per agent and dose. We deem it unlikely that improved lipid levels are sufficient to explain the beneficial effects of GLP-1RA on cardiovascular risk, especially given the improvement of many other risk factors (body weight, glycemic control, inflammation) while using these agents. Posthoc mediation analyses of large cardiovascular outcome trials may shed some light on the relative importance of each risk factor.

Summary: GLP-1RAs improve lipid profiles in clinical trials, but their complete cardiovascular benefits likely involve multifactorial mechanisms beyond lipid modulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / metabolism
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Humans
  • Incretins* / therapeutic use
  • Lipids / blood

Substances

  • Incretins
  • Glucagon-Like Peptide-1 Receptor
  • Lipids
  • Glucagon-Like Peptide-1 Receptor Agonists