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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BMC
2025-08-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-025-01878-3 |
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| author | Baixuan Shen Wanying Wang Yuanhui Guo Zilong Chen Chuanxin Liu Jiarui Huang Ying Li |
| author_facet | Baixuan Shen Wanying Wang Yuanhui Guo Zilong Chen Chuanxin Liu Jiarui Huang Ying Li |
| author_sort | Baixuan Shen |
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| description | 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. |
| format | Article |
| id | doaj-art-b19bb7fa2b5c4b9782eab83915e2b1c5 |
| institution | Kabale University |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-b19bb7fa2b5c4b9782eab83915e2b1c52025-08-24T11:41:40ZengBMCDiabetology & Metabolic Syndrome1758-59962025-08-0117111710.1186/s13098-025-01878-3Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populationsBaixuan Shen0Wanying Wang1Yuanhui Guo2Zilong Chen3Chuanxin Liu4Jiarui Huang5Ying Li6Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan, University of Science and TechnologyLuoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan, University of Science and TechnologyLuoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan, University of Science and TechnologyLuoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan, University of Science and TechnologyLuoyang Key Laboratory of Clinical Multiomics and Translational Medicine, Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital, and College of Clinical Medicine of Henan, University of Science and TechnologyDepartment of Internal Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and TechnologyDepartment of Pharmacy, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and TechnologyAbstract 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.https://doi.org/10.1186/s13098-025-01878-3GLP-1R agonistDiabetic retinopathyMendelian randomizationSingle nucleotide polymorphismsGenome-wide association studies |
| spellingShingle | Baixuan Shen Wanying Wang Yuanhui Guo Zilong Chen Chuanxin Liu Jiarui Huang Ying Li Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations Diabetology & Metabolic Syndrome GLP-1R agonist Diabetic retinopathy Mendelian randomization Single nucleotide polymorphisms Genome-wide association studies |
| title | Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations |
| title_full | Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations |
| title_fullStr | Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations |
| title_full_unstemmed | Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations |
| title_short | Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations |
| title_sort | understanding the risk of diabetic retinopathy from glucagon like peptide 1 receptor agonists a mendelian randomization study and systematic review of european populations |
| topic | GLP-1R agonist Diabetic retinopathy Mendelian randomization Single nucleotide polymorphisms Genome-wide association studies |
| url | https://doi.org/10.1186/s13098-025-01878-3 |
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