Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations
Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RA) are extensively prescribed to treat obesity and diabetes. However, previous studies have debated whether GLP-1RA use induces diabetic retinopathy (DR) in diabetic populations, and the relationship between the two is unclear. Met...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-08-01
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| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13098-025-01878-3 |
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| Summary: | Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RA) are extensively prescribed to treat obesity and diabetes. However, previous studies have debated whether GLP-1RA use induces diabetic retinopathy (DR) in diabetic populations, and the relationship between the two is unclear. Methods Cis-expressed quantitative trait locus data (Cis-eQTL) in blood tissue were used to extract single nucleotide polymorphisms (SNPs) as a genetic proxy tool. The analyses were performed using Mendelian randomisation (MR) as the primary tool and Summary-data-based Mendelian Randomization (SMR) as an auxiliary validation. Discovery cohort was obtained from a large study from the GWAS catalog database, and the FinnGen consortium DR data were used as a validation cohort. Additionally, the outcomes of the two cohorts were combined using meta-analysis. In addition, we systematically retrieved relevant cohort studies of GLP-1RA and DR for systematic review to complement the association of GLP-1RA with DR in the real world. Results A total of 9 SNPs highly correlated with the exposure were screened as tool variables to proxy for GLP-1RA. The MR method showed a significant association between GLP-1RA and reduced risk of DR (OR = 0.59, 95%CI: 0.39–0.89, P = 0.0109), in addition, similar results were also found with the SMR method (OR = 0.48, 95%CI: 0.27–0.86, P = 0.0129). Finally, a total of three eligible articles were included in the systematic review, and overall GLP-1RA reduces the incidence of DR compared with existing glucose-lowering agents, but more research is required to verify the generalisability of the findings. Conclusion Based on MR and SMR, we found that GLP-1RA can reduce the risk of DR. Systematic review showed that compared with insulin therapy, T2D patients treated with GLP-1RA had a lower incidence of DR, but compared with other hypoglycemic agents, the incidence of DR was inconsistent. Therefore, clinical trials with larger sample sizes and longer follow-up times are warranted to determine this. |
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| ISSN: | 1758-5996 |