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Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization studies
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Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization studies
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Journal Article
Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization studies
2023
Overview
Background
The ability of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to decrease certain microvascular events has called for the investigation of GLP-1 RAs against diabetic retinopathy (DR), but the evidence is limited. By combining data from observational and Mendelian randomization (MR) studies, we aimed to investigate whether GLP-1 RAs decrease the risk of DR.
Methods
We combined data from several Swedish Registers and identified patients with incident type 2 diabetes being treated with GLP-1 RAs between 2006 and 2015, and matched them to diabetic patients who did not use GLP-1 RAs as the comparisons. The Cox proportional hazards models were applied to assess the risk of DR. We further performed the summary-data-based MR (SMR) analyses based on the Genotype-Tissue Expression databases and the Genome-Wide Association Study of DR from the FinnGen consortium.
Results
A total of 2390 diabetic patients were treated with GLP-1 RAs and the incidence of DR was 5.97 per 1000 person-years. Compared with diabetic patients who did not use GLP-1 RAs having an incidence of 12.85 per 1000 person-years, the adjusted hazard ratio (HR) of DR was 0.42 [95% confidence interval (CI), 0.29–0.61]. Genetically-predicted
GLP1R
expression (the target of GLP-1 RAs) showed an inverse association with background [odds ratio (OR)=0.83, 95% CI, 0.71–0.97] and severe nonproliferative DR (OR=0.72, 95% CI, 0.53–0.98), and a non-significant association with overall (OR=0.97, 95% CI, 0.92–1.03) and proliferative DR (OR=0.98, 95% CI, 0.91–1.05).
Conclusions
Both observational and mendelian randomization analyses showed a significantly lower risk of DR for patients treated with GLP-1 RAs, which calls for further studies to validate these findings.
Publisher
Springer Science and Business Media LLC,BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Analysis
/ Codes
/ Diabetes
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - complications
/ Diabetes Mellitus, Type 2 - drug therapy
/ Diabetes Mellitus, Type 2 - genetics
/ Diabetic Retinopathy - chemically induced
/ Diabetic Retinopathy - epidemiology
/ Diabetic Retinopathy - genetics
/ Genome-wide association studies
/ Genome-Wide Association Study
/ Genomes
/ Glucagon
/ Glucagon-Like Peptide-1 Receptor
/ Glucagon-Like Peptide-1 Receptor - agonists
/ Glucagon-Like Peptide-1 Receptor - genetics
/ Humans
/ Medicine
/ Mendelian Randomization Analysis
/ Patients
/ Peptides
/ R
/ Retina
