Genetic evidence for repurposing of glucagon-like peptide-1 receptor agonists to prevent heart failure
File(s)
Published version
Author(s)
Gill, Dipender
Type
Journal Article
Abstract
Background: To investigate the genetic evidence for repurposing of glucagon-like peptide-1 receptor (GLP1R) agonists to prevent heart failure (HF) and whether the potential benefit exceeds the benefit conferred by more general glycemic control. Methods and Results: We applied two-sample Mendelian randomization of genetically proxied GLP1R agonism on HF as the main outcome and left ventricular ejection fraction (LVEF) as the secondary outcome. The associations were compared to those of general glycemic control on the same outcomes. Genetic associations were obtained from genome-wide association study summary statistics of type 2 diabetes (228,499 cases and 1,178,783 controls), glycated hemoglobin (n=344,182), HF (47,309 cases and 930,014 controls), and LVEF (n=16,923). Genetic proxies for GLP1R agonism associated with reduced risk of HF (odds ratio per 1mmol/mol decrease in glycated hemoglobin 0.75, 95% confidence interval 0.64-0.87, P=1.69x10-4), and higher LVEF (standard deviation change in LVEF per 1mmol/mol decrease in glycated hemoglobin 0.22, 95% confidence interval 0.03-0.42, P=0.03). The magnitude of these benefits exceeded those expected from improved glycemic control more generally. The results were similar in sensitivity analyses, and we did not find evidence to suggest that these associations were mediated by reduced coronary artery disease risk. Conclusions: This genetic evidence supports the re-purposing of GLP1R agonists for preventing HF.
Date Issued
2021-06-29
Date Acceptance
2021-05-03
Citation
Journal of the American Heart Association, 2021, 10 (13)
ISSN
2047-9980
Publisher
Wiley
Journal / Book Title
Journal of the American Heart Association
Volume
10
Issue
13
Copyright Statement
© 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative
Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
JAHA is available at: www.ahajournals.org/journal/jaha
Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
JAHA is available at: www.ahajournals.org/journal/jaha
License URL
Identifier
https://www.ahajournals.org/doi/10.1161/JAHA.120.020331
Subjects
Science & Technology
Life Sciences & Biomedicine
Cardiac & Cardiovascular Systems
Cardiovascular System & Cardiology
diabetes mellitus
ejection fraction
GLP1R
heart failure
Mendelian randomization
MENDELIAN RANDOMIZATION
GLP1R
Mendelian randomization
diabetes mellitus
ejection fraction
heart failure
1102 Cardiorespiratory Medicine and Haematology
Publication Status
Published
Date Publish Online
2021-06-29