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Glucagon-like peptide-1 receptor agonists and diabetic retinopathy: nationwide cohort and Mendelian randomization

Deqiang Zheng1,2, Ning Li1, Rui Hou1

  • 1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.

BMC Medicine
|February 4, 2023
PubMed
Abstract

Insights

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduce the risk of diabetic retinopathy (DR). Both observational and genetic studies confirm that GLP-1 RAs offer protection against DR development.

Area of Science:

  • Endocrinology
  • Ophthalmology
  • Pharmacology

Background:

  • Diabetic retinopathy (DR) is a leading cause of vision loss in diabetic patients.
  • Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown potential in reducing microvascular events.
  • Limited evidence exists on the efficacy of GLP-1 RAs in preventing DR.

Purpose of the Study:

  • To investigate the potential of GLP-1 RAs in reducing the risk of diabetic retinopathy (DR).
  • To combine observational and Mendelian randomization (MR) data for a comprehensive analysis.

Main Methods:

  • Retrospective cohort study using Swedish Registers (2006-2015) comparing GLP-1 RA users with non-users.
  • Cox proportional hazards models to assess DR risk.
  • Summary-data-based Mendelian randomization (SMR) analyses using Genotype-Tissue Expression and FinnGen consortium data.

Main Results:

  • Observational data: GLP-1 RA users had a 58% lower risk of DR (HR=0.42, 95% CI 0.29-0.61).
  • Mendelian randomization: Higher genetically predicted GLP1R expression associated with lower odds of background DR (OR=0.83) and severe nonproliferative DR (OR=0.72).
  • No significant association found for overall or proliferative DR in MR analyses.

Conclusions:

  • Both observational and Mendelian randomization studies suggest GLP-1 RAs significantly lower the risk of diabetic retinopathy.
  • These findings highlight the potential protective role of GLP-1 RAs against DR.
  • Further research is warranted to validate these promising results.
Keywords:
Cohort studyDiabetic retinopathyGLP-1 RAsMendelian randomization

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