PDF(Pubmed)
Abstract：
BACKGROUND: The incidence of diabetic gastrointestinal diseases is increasing year by year. This study aimed to investigate the causal relationship between antidiabetic medications and gastrointestinal disorders, with the goal of reducing the incidence of diabetes-related gastrointestinal diseases and exploring the potential repurposing of antidiabetic drugs.
METHODS: We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn\'s disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control.
RESULTS: Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10- 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10- 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10- 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10- 2).
CONCLUSIONS: The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.
METHODS: We employed a two-sample Mendelian randomization (TSMR) design to investigate the causal association between antidiabetic medications and gastrointestinal disorders, including gastroesophageal reflux disease (GERD), gastric ulcer (GU), chronic gastritis, acute gastritis, Helicobacter pylori infection, gastric cancer (GC), functional dyspepsia (FD), irritable bowel syndrome (IBS), ulcerative colitis (UC), Crohn\'s disease (CD), diverticulosis, and colorectal cancer (CRC). To identify potential inhibitors of antidiabetic drug targets, we collected single-nucleotide polymorphisms (SNPs) associated with metformin, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, insulin, and its analogs, thiazolidinediones, sulfonylureas, and alpha-glucosidase inhibitors from published genome-wide association study statistics. We then conducted a drug-target Mendelian randomization (MR) analysis using inverse variance weighting (IVW) as the primary analytical method to assess the impact of these inhibitors on gastrointestinal disorders. Additionally, diabetes was selected as a positive control.
RESULTS: Sulfonylureas were found to significantly reduce the risk of CD (IVW: OR [95% CI] = 0.986 [0.978, 0.995], p = 1.99 × 10- 3), GERD (IVW: OR [95% CI] = 0.649 [0.452, 0.932], p = 1.90 × 10- 2), and chronic gastritis (IVW: OR [95% CI] = 0.991 [0.982, 0.999], p = 4.50 × 10- 2). However, they were associated with an increased risk of GU development (IVW: OR [95%CI] = 2 0.761 [1.259, 6.057], p = 1 0.12 × 10- 2).
CONCLUSIONS: The results indicated that sulfonylureas had a positive effect on the prevention of CD, GERD, and chronic gastritis but a negative effect on the development of gastric ulcers. However, our research found no causal evidence for the impact of metformin, GLP-1 agonists, SGLT2 inhibitors, DPP 4 inhibitors, insulin and its analogs, thiazolidinediones, or alpha-glucosidase inhibitors on gastrointestinal diseases.
摘要：
背景：糖尿病胃肠道疾病的发病率呈逐年上升趋势。本研究旨在探讨抗糖尿病药物与胃肠道疾病之间的因果关系，目的是降低糖尿病相关胃肠道疾病的发生率，并探索抗糖尿病药物的潜在用途。
方法：我们采用双样本孟德尔随机化（TSMR）设计来研究抗糖尿病药物与胃肠道疾病之间的因果关系，包括胃食管反流病（GERD），胃溃疡（GU），慢性胃炎,急性胃炎,幽门螺杆菌感染,胃癌（GC），功能性消化不良（FD），肠易激综合征（IBS），溃疡性结肠炎（UC），克罗恩病（CD），憩室病,结直肠癌（CRC）。为了确定抗糖尿病药物靶点的潜在抑制剂，我们收集了与二甲双胍相关的单核苷酸多态性（SNPs），GLP-1受体激动剂,SGLT2抑制剂，DPP-4抑制剂，胰岛素，和它的类似物，噻唑烷二酮，磺酰脲类,和α-葡萄糖苷酶抑制剂来自已发表的全基因组关联研究统计数据。然后，我们使用方差逆加权（IVW）作为主要分析方法进行了药物靶向孟德尔随机化（MR）分析，以评估这些抑制剂对胃肠道疾病的影响。此外,选择糖尿病作为阳性对照.
结果：发现磺脲类药物显着降低CD的风险（IVW：OR[95％CI]=0.986[0.978，0.995]，p=1.99×10-3)，GERD（IVW：或[95%CI]=0.649[0.452，0.932]，p=1.90×10-2)，和慢性胃炎（IVW：OR[95%CI]=0.991[0.982,0.999]，p=4.50×10-2)。然而,它们与GU发展的风险增加相关(IVW：OR[95CI]=20.761[1.259，6.057]，p=10.12×10-2)。
结论：结果表明，磺脲类药物对预防CD具有积极作用，GERD,和慢性胃炎，但对胃溃疡的发展有负面影响。然而,我们的研究没有发现二甲双胍影响的因果证据，GLP-1激动剂,SGLT2抑制剂，DPP4抑制剂，胰岛素及其类似物，噻唑烷二酮，或对胃肠道疾病的α-葡萄糖苷酶抑制剂。
方法：我们采用双样本孟德尔随机化（TSMR）设计来研究抗糖尿病药物与胃肠道疾病之间的因果关系，包括胃食管反流病（GERD），胃溃疡（GU），慢性胃炎,急性胃炎,幽门螺杆菌感染,胃癌（GC），功能性消化不良（FD），肠易激综合征（IBS），溃疡性结肠炎（UC），克罗恩病（CD），憩室病,结直肠癌（CRC）。为了确定抗糖尿病药物靶点的潜在抑制剂，我们收集了与二甲双胍相关的单核苷酸多态性（SNPs），GLP-1受体激动剂,SGLT2抑制剂，DPP-4抑制剂，胰岛素，和它的类似物，噻唑烷二酮，磺酰脲类,和α-葡萄糖苷酶抑制剂来自已发表的全基因组关联研究统计数据。然后，我们使用方差逆加权（IVW）作为主要分析方法进行了药物靶向孟德尔随机化（MR）分析，以评估这些抑制剂对胃肠道疾病的影响。此外,选择糖尿病作为阳性对照.
结果：发现磺脲类药物显着降低CD的风险（IVW：OR[95％CI]=0.986[0.978，0.995]，p=1.99×10-3)，GERD（IVW：或[95%CI]=0.649[0.452，0.932]，p=1.90×10-2)，和慢性胃炎（IVW：OR[95%CI]=0.991[0.982,0.999]，p=4.50×10-2)。然而,它们与GU发展的风险增加相关(IVW：OR[95CI]=20.761[1.259，6.057]，p=10.12×10-2)。
结论：结果表明，磺脲类药物对预防CD具有积极作用，GERD,和慢性胃炎，但对胃溃疡的发展有负面影响。然而,我们的研究没有发现二甲双胍影响的因果证据，GLP-1激动剂,SGLT2抑制剂，DPP4抑制剂，胰岛素及其类似物，噻唑烷二酮，或对胃肠道疾病的α-葡萄糖苷酶抑制剂。
