使用 DPP4 抑制剂和 GLP-1 受体激动剂与肠梗阻风险：斯堪的纳维亚队列研究。
Use of DPP4 Inhibitors and GLP-1 Receptor Agonists and Risk of Intestinal Obstruction: Scandinavian Cohort Study.
机构信息
Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
出版信息
Clin Gastroenterol Hepatol. 2024 Jun;22(6):1226-1237.e14. doi: 10.1016/j.cgh.2023.08.034. Epub 2023 Sep 15.
BACKGROUND & AIMS: Concerns have been raised that the incretin-based diabetes drugs dipeptidyl peptidase 4 (DPP4) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists may increase the risk of intestinal obstruction. We aimed to assess the association between use of DPP4 inhibitors and GLP-1 receptor agonists and the risk of intestinal obstruction.
METHODS
Using data from nationwide registers in Sweden, Denmark, and Norway, 2013-2021, we conducted 2 cohort studies, one for DPP4 inhibitors and one for GLP-1 receptor agonists, to investigate the risk of intestinal obstruction as compared with an active comparator drug class (sodium-glucose co-transporter 2 [SGLT2] inhibitors).
RESULTS
Among 19,0321 new users of DPP4 inhibitors (median (interquartile range [IQR]) follow-up time, 1.3 [0.6-2.6] years) and 139,315 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.7] years), 919 intestinal obstruction events occurred. Use of DPP4 inhibitors, as compared with SGLT2 inhibitors, was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 2.0 vs 1.8 per 1000 person-years; hazard ratio, 1.13; 95% confidence interval, 0.96-1.34). Among 121,254 new users of GLP-1 receptor agonists (median [standard deviation] follow-up time, 0.9 [0.4-1.9] years) and 185,027 new users of SGLT2 inhibitors (median [IQR] follow-up time, 0.8 [0.4-1.8] years), 557 intestinal obstruction events occurred. Use of GLP-1 receptor agonists was not associated with a statistically significant increase in risk of intestinal obstruction (adjusted incidence rate, 1.3 vs 1.6 per 1000 person-years; hazard ratio, 0.83; 95% confidence interval, 0.69-1.01).
CONCLUSIONS
In this analysis of nationwide data from 3 countries, previous safety signals indicating an increased risk of intestinal obstruction with use of DPP4 inhibitors and GLP-1 receptor agonists were not confirmed.
背景与目的
人们担心基于肠促胰岛素的糖尿病药物二肽基肽酶 4（DPP4）抑制剂和胰高血糖素样肽 1（GLP-1）受体激动剂可能会增加肠梗阻的风险。我们旨在评估 DPP4 抑制剂和 GLP-1 受体激动剂的使用与肠梗阻风险之间的关联。
方法
我们使用来自瑞典、丹麦和挪威的全国性登记处的数据，在 2013 年至 2021 年期间进行了两项队列研究，一项针对 DPP4 抑制剂，一项针对 GLP-1 受体激动剂，以比较与活性对照药物类别（钠-葡萄糖共转运蛋白 2 [SGLT2] 抑制剂）相比，评估肠梗阻的风险。
结果
在 190321 例新使用 DPP4 抑制剂（中位[四分位距（IQR）]随访时间 1.3[0.6-2.6]年）和 139315 例新使用 SGLT2 抑制剂（中位[IQR]随访时间 0.8[0.4-1.7]年）的患者中，发生了 919 例肠梗阻事件。与 SGLT2 抑制剂相比，DPP4 抑制剂的使用与肠梗阻风险的统计学显著增加无关（调整后的发病率，每 1000 人年 2.0 与 1.8；危险比，1.13；95%置信区间，0.96-1.34）。在 121254 例新使用 GLP-1 受体激动剂（中位[标准差]随访时间 0.9[0.4-1.9]年）和 185027 例新使用 SGLT2 抑制剂（中位[IQR]随访时间 0.8[0.4-1.8]年）的患者中，发生了 557 例肠梗阻事件。使用 GLP-1 受体激动剂与肠梗阻风险的统计学显著增加无关（调整后的发病率，每 1000 人年 1.3 与 1.6；危险比，0.83；95%置信区间，0.69-1.01）。
结论
在这项来自 3 个国家的全国性数据分析中，先前的安全性信号表明 DPP4 抑制剂和 GLP-1 受体激动剂的使用会增加肠梗阻的风险，但没有得到证实。
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