Shen Baixuan, Wang Wanying, Guo Yuanhui, Chen Zilong, Liu Chuanxin, Huang Jiarui, Li Ying
Luoyang 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 Technology, Luoyang, 471003, China.
Department of Internal Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
Diabetol Metab Syndr. 2025 Aug 20;17(1):345. doi: 10.1186/s13098-025-01878-3.
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, = 0.0109), in addition, similar results were also found with the SMR method (OR = 0.48, 95%CI: 0.27–0.86, = 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-025-01878-3.
背景：胰高血糖素样肽-1受体激动剂（GLP-1RA）被广泛用于治疗肥胖症和糖尿病。然而，先前的研究对GLP-1RA的使用是否会在糖尿病患者中诱发糖尿病视网膜病变（DR）存在争议，两者之间的关系尚不清楚。 方法：利用血液组织中的顺式表达定量性状位点数据（Cis-eQTL）提取单核苷酸多态性（SNP）作为遗传代理工具。分析以孟德尔随机化（MR）作为主要工具，基于汇总数据的孟德尔随机化（SMR）作为辅助验证。发现队列来自GWAS目录数据库的一项大型研究，FinnGen联盟的DR数据用作验证队列。此外，使用荟萃分析将两个队列的结果合并。另外，我们系统检索了GLP-1RA与DR的相关队列研究进行系统评价，以补充GLP-1RA与DR在现实世界中的关联。 结果：总共筛选出9个与暴露高度相关的SNP作为代理GLP-1RA的工具变量。MR方法显示GLP-1RA与DR风险降低之间存在显著关联（OR = 0.59，95%CI：0.39–0.89，P = 0.0109），此外，SMR方法也发现了类似结果（OR = 0.48，95%CI：0.27–0.86，P = 0.0129）。最后，系统评价共纳入3篇符合条件的文章，总体而言，与现有的降糖药物相比，GLP-1RA降低了DR的发生率，但需要更多研究来验证这些发现的普遍性。 结论：基于MR和SMR，我们发现GLP-1RA可降低DR风险。系统评价显示，与胰岛素治疗相比，接受GLP-1RA治疗的2型糖尿病患者DR发生率较低，但与其他降糖药物相比，DR发生率不一致。因此，有必要进行更大样本量和更长随访时间的临床试验来确定这一点。 补充信息：在线版本包含可在10.1186/s13098-025-01878-3获取的补充材料。
ESC Heart Fail. 2025-4-28
Mol Biol Rep. 2025-4-10
Ophthalmology. 2025-2-18
Diabetes Care. 2025-1-1
Pharmacotherapy. 2024-9
Front Endocrinol (Lausanne). 2024-7-24
Lancet Diabetes Endocrinol. 2024-9
Zotero 插件
