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Background <p>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.</p> Methods <p>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.</p> Results <p>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, <i>P</i> = 0.0109), in addition, similar results were also found with the SMR method (OR = 0.48, 95%CI: 0.27–0.86, <i>P</i> = 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.</p> Conclusion <p>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.</p>

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Understanding the risk of diabetic retinopathy from glucagon-like peptide-1 receptor agonists: a Mendelian randomization study and systematic review of European populations

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月20日

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  • Baixuan Shen,
  • Wanying Wang,
  • Yuanhui Guo,
  • Zilong Chen,
  • Chuanxin Liu,
  • Jiarui Huang,
  • Ying Li

摘要

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.