Sijia Lai, Yaohui Feng, Lu Li, Jiayu Zhao, Zhenyu Wang, Yanli Wang
{"title":"GLP1RAs与慢性阻塞性肺疾病风险的关联：来自药物靶孟德尔随机化的证据","authors":"Sijia Lai, Yaohui Feng, Lu Li, Jiayu Zhao, Zhenyu Wang, Yanli Wang","doi":"10.1186/s13098-025-01866-7","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Glucose-lowering glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used to treat type 2 diabetes (T2D) and obesity. However, their potential benefits in pulmonary diseases remain unclear. To address this, we used Mendelian randomization (MR) analysis to assess the causal effects of genetically proxied GLP1RAs on chronic obstructive pulmonary disease (COPD) and related conditions, including bronchitis and asthma.</p><p><strong>Methods: </strong>We selected cis-expression quantitative trait loci (cis-eQTLs) as instrumental variables to genetically proxy GLP1RAs. Summary-level data were obtained from the eQTLGen and FinnGen consortia. MR analyses were used to identify the association between genetically proxied GLP1RAs and COPD, as well as COPD-related diseases. T2D, HbA1c levels, and BMI were used as positive controls.</p><p><strong>Results: </strong>After Benjamini-Hochberg correction for multiple testing, MR analyses indicated that genetically predicted GLP1RAs were significantly associated with lower risks of COPD (OR [95% CI] = 0.838 [0.74-0.948], P = 0.013), early-onset COPD (< 65 years) (OR [95% CI] = 0.751[0.622-0.906], P = 0.01), COPD-related respiratory insufficiency (OR [95% CI] = 0.720[0.55-0.944], P = 0.024), acute bronchitis (OR [95% CI] = 0.787 [0.693-0.893], P = 0.002), asthma (OR [95% CI] = 0.872 [0.782-0.973], P = 0.023), and other symptoms and signs involving the circulatory and respiratory systems (OR [95% CI] = 0.426 [0.217-0.834], P = 0.023). No significant association was observed for later-onset COPD (≥ 65 years) (OR [95% CI] = 0.921 [0.783-1.082], P = 0.315) or chronic bronchitis risk (OR [95% CI] = 0.950 [0.889-1.016], P = 0.146).</p><p><strong>Conclusions: </strong>Genetically predicted GLP1RAs are associated with a lower risk of early-onset COPD, COPD-related respiratory insufficiency, acute bronchitis, and asthma. These findings highlight potential benefits of GLP1RAs in T2D patients with coexisting pulmonary diseases and support the need for further investigation in COPD management.</p>","PeriodicalId":11106,"journal":{"name":"Diabetology & Metabolic Syndrome","volume":"17 1","pages":"295"},"PeriodicalIF":3.9000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302747/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association of GLP1RAs with risk of chronic obstructive pulmonary disease: evidence from drug target Mendelian randomization.\",\"authors\":\"Sijia Lai, Yaohui Feng, Lu Li, Jiayu Zhao, Zhenyu Wang, Yanli Wang\",\"doi\":\"10.1186/s13098-025-01866-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Glucose-lowering glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used to treat type 2 diabetes (T2D) and obesity. However, their potential benefits in pulmonary diseases remain unclear. To address this, we used Mendelian randomization (MR) analysis to assess the causal effects of genetically proxied GLP1RAs on chronic obstructive pulmonary disease (COPD) and related conditions, including bronchitis and asthma.</p><p><strong>Methods: </strong>We selected cis-expression quantitative trait loci (cis-eQTLs) as instrumental variables to genetically proxy GLP1RAs. Summary-level data were obtained from the eQTLGen and FinnGen consortia. MR analyses were used to identify the association between genetically proxied GLP1RAs and COPD, as well as COPD-related diseases. T2D, HbA1c levels, and BMI were used as positive controls.</p><p><strong>Results: </strong>After Benjamini-Hochberg correction for multiple testing, MR analyses indicated that genetically predicted GLP1RAs were significantly associated with lower risks of COPD (OR [95% CI] = 0.838 [0.74-0.948], P = 0.013), early-onset COPD (< 65 years) (OR [95% CI] = 0.751[0.622-0.906], P = 0.01), COPD-related respiratory insufficiency (OR [95% CI] = 0.720[0.55-0.944], P = 0.024), acute bronchitis (OR [95% CI] = 0.787 [0.693-0.893], P = 0.002), asthma (OR [95% CI] = 0.872 [0.782-0.973], P = 0.023), and other symptoms and signs involving the circulatory and respiratory systems (OR [95% CI] = 0.426 [0.217-0.834], P = 0.023). No significant association was observed for later-onset COPD (≥ 65 years) (OR [95% CI] = 0.921 [0.783-1.082], P = 0.315) or chronic bronchitis risk (OR [95% CI] = 0.950 [0.889-1.016], P = 0.146).</p><p><strong>Conclusions: </strong>Genetically predicted GLP1RAs are associated with a lower risk of early-onset COPD, COPD-related respiratory insufficiency, acute bronchitis, and asthma. These findings highlight potential benefits of GLP1RAs in T2D patients with coexisting pulmonary diseases and support the need for further investigation in COPD management.</p>\",\"PeriodicalId\":11106,\"journal\":{\"name\":\"Diabetology & Metabolic Syndrome\",\"volume\":\"17 1\",\"pages\":\"295\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-07-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12302747/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Diabetology & Metabolic Syndrome\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s13098-025-01866-7\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetology & Metabolic Syndrome","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13098-025-01866-7","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Association of GLP1RAs with risk of chronic obstructive pulmonary disease: evidence from drug target Mendelian randomization.
Background: Glucose-lowering glucagon-like peptide-1 receptor agonists (GLP1RAs) are widely used to treat type 2 diabetes (T2D) and obesity. However, their potential benefits in pulmonary diseases remain unclear. To address this, we used Mendelian randomization (MR) analysis to assess the causal effects of genetically proxied GLP1RAs on chronic obstructive pulmonary disease (COPD) and related conditions, including bronchitis and asthma.
Methods: We selected cis-expression quantitative trait loci (cis-eQTLs) as instrumental variables to genetically proxy GLP1RAs. Summary-level data were obtained from the eQTLGen and FinnGen consortia. MR analyses were used to identify the association between genetically proxied GLP1RAs and COPD, as well as COPD-related diseases. T2D, HbA1c levels, and BMI were used as positive controls.
Results: After Benjamini-Hochberg correction for multiple testing, MR analyses indicated that genetically predicted GLP1RAs were significantly associated with lower risks of COPD (OR [95% CI] = 0.838 [0.74-0.948], P = 0.013), early-onset COPD (< 65 years) (OR [95% CI] = 0.751[0.622-0.906], P = 0.01), COPD-related respiratory insufficiency (OR [95% CI] = 0.720[0.55-0.944], P = 0.024), acute bronchitis (OR [95% CI] = 0.787 [0.693-0.893], P = 0.002), asthma (OR [95% CI] = 0.872 [0.782-0.973], P = 0.023), and other symptoms and signs involving the circulatory and respiratory systems (OR [95% CI] = 0.426 [0.217-0.834], P = 0.023). No significant association was observed for later-onset COPD (≥ 65 years) (OR [95% CI] = 0.921 [0.783-1.082], P = 0.315) or chronic bronchitis risk (OR [95% CI] = 0.950 [0.889-1.016], P = 0.146).
Conclusions: Genetically predicted GLP1RAs are associated with a lower risk of early-onset COPD, COPD-related respiratory insufficiency, acute bronchitis, and asthma. These findings highlight potential benefits of GLP1RAs in T2D patients with coexisting pulmonary diseases and support the need for further investigation in COPD management.
期刊介绍：
Diabetology & Metabolic Syndrome publishes articles on all aspects of the pathophysiology of diabetes and metabolic syndrome.
By publishing original material exploring any area of laboratory, animal or clinical research into diabetes and metabolic syndrome, the journal offers a high-visibility forum for new insights and discussions into the issues of importance to the relevant community.
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