Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms

of action

Author(s)
Ussher, John R.,Drucker, Daniel J.

Publisher
Springer Nature

Source
Crossref Journals

Publication name
Nature Reviews Cardiology

Volume
20

Issue
7

Pages
463-474

Start page
463

Language(s)
English

Subject(s)
Diabetes Mellitus, Type 2,Cardiovascular System,Cardiovascular Diseases,Hypoglycemic
Agents,Glucagon-Like Peptide 1,Glucagon-Like Peptide-1 Receptor

Publication location
England

Date
2023/07/01

doi
10.1038/s41569-023-00849-3

pmid
36977782

Description / abstract
Type 2 diabetes mellitus (T2DM) and obesity are metabolic disorders characterized by excess
cardiovascular risk. Glucagon-like peptide 1 (GLP1) receptor (GLP1R) agonists reduce body
weight, glycaemia, blood pressure, postprandial lipaemia and inflammation - actions that could
contribute to the reduction of cardiovascular events. Cardiovascular outcome trials (CVOTs) have
demonstrated that GLP1R agonists reduce the rates of major adverse cardiovascular events in
patients with T2DM. Separate phase III CVOTs of GLP1R agonists are currently being conducted
in people living with heart failure with preserved ejection fraction and in those with obesity.
Mechanistically, GLP1R is expressed at low levels in the heart and vasculature, raising the
possibility that GLP1 might have both direct and indirect actions on the cardiovascular system. In
this Review, we summarize the data from CVOTs of GLP1R agonists in patients with T2DM and
describe the actions of GLP1R agonists on the heart and blood vessels. We also assess the
potential mechanisms that contribute to the reduction in major adverse cardiovascular events in
individuals treated with GLP1R agonists and highlight the emerging cardiovascular biology of
novel GLP1-based multi-agonists currently in development. Understanding how GLP1R signalling
protects the heart and blood vessels will optimize the therapeutic use and development of next-
generation GLP1-based therapies with improved cardiovascular safety.