Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes Mellitus
Association of Bile Duct and Gallbladder Diseases With the Use of Incretin-Based Drugs in Patients With Type 2 Diabetes Mellitus
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DOI：
10.1001/jamainternmed.2016.1531
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发表时间：
2016-10-01
影响因子：
39
通讯作者：
Azoulay, Laurent
中科院分区：
文献类型：
--
作者：
Faillie, Jean-Luc;Yu, Oriana H.;Azoulay, Laurent
重要性二肽基肽酶-4（DPP-4）抑制剂和胰高血糖素样肽1（GLP-1）类似物（一组用于治疗2型糖尿病的药物）的使用可能与胆管和胆囊疾病的风险增加相关。迄今为止，还没有观察性研究评估这种可能的association.Objective确定DPP-4抑制剂和GLP-1类似物的使用是否与2型糖尿病患者胆管和胆囊疾病的风险增加有关。设计，设置和参与者一项基于人群的队列研究，将英国临床实践研究数据链与医院EpperimentStatistics数据库联系起来，产生了71369名18岁或以上患者的队列，开始使用抗糖尿病药物（包括口服和注射剂），2007年1月1日至3月31日，2014.披露DPP-4抑制剂和GLP-1类似物的当前使用（单独或联合治疗）与目前使用至少2种口服降糖药相比。使用依赖性考克斯比例风险模型估计胆管或胆囊事件的风险比（HR）和95% CI（胆石症、胆囊炎、胆管炎）导致住院，比较目前使用DPP-4抑制剂和GLP-1类似物与目前使用至少2种口服降糖药的情况。结果在227994人-年的随访中，71369例患者中有853例因胆管和胆囊疾病住院（发病率/1000人-年，3.7; 95% CI，3.5-4.0）。与目前使用至少2种口服降糖药相比，目前使用DPP-4抑制剂与胆管和胆囊疾病风险增加无关（3.6 vs 3.3/1000人-年;校正HR，0.99; 95% CI，0.75-1.32）。相比之下，与目前使用至少2种口服降糖药相比，使用GLP-1类似物与胆管和胆囊疾病风险增加相关（6.1 vs 3.3/1000人-年;校正HR，1.79; 95% CI，1.21-2.67）。在二次分析中，GLP-1类似物也与胆囊切除术风险增加相关（校正HR，2.08; 95%CI，1.08-4.02）。结论和相关性GLP-1类似物的使用与胆管和胆囊疾病风险增加相关。医生在处方这些药物时应了解这种潜在的不良事件。
IMPORTANCE The use of dipeptidyl-peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) analogues-a group of drugs used in the management of type 2 diabetes mellitus-may be associated with an increased risk of bile duct and gallbladder disease. To date, no observational study has assessed this possible association.OBJECTIVE To determine whether the use of DPP-4 inhibitors and GLP-1 analogues is associated with an increased risk of incident bile duct and gallbladder disease in patients with type 2 diabetes.DESIGN, SETTING, AND PARTICIPANTS A population-based cohort study linked the United Kingdom Clinical Practice Research Datalink with the Hospital Episodes Statistics database, yielding a cohort of 71 369 patients, 18 years or older, initiating an antidiabetic drug (including oral and injectable agents) between January 1, 2007, and March 31, 2014.EXPOSURES Current use of DPP-4 inhibitors and GLP-1 analogues (alone or in combination therapy) compared with current use of at least 2 oral antidiabetic drugs.MAIN OUTCOMES AND MEASURES Time-dependent Cox proportional hazards models were used to estimate hazard ratios (HRs) with 95% CIs of incident bile duct or gallbladder events (cholelithiasis, cholecystitis, cholangitis) causing hospitalization, comparing current use of DPP-4 inhibitors and GLP-1 analogues with current use of at least 2 oral antidiabetic drugs.RESULTS During 227 994 person-years of follow-up, 853 of the 71 369 patients were hospitalized for bile duct and gallbladder disease (incidence rate per 1000 person-years, 3.7; 95% CI, 3.5-4.0). Current use of DPP-4 inhibitors was not associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (3.6 vs 3.3 per 1000 person-years; adjusted HR, 0.99; 95% CI, 0.75-1.32). In contrast, the use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease compared with current use of at least 2 oral antidiabetic drugs (6.1 vs 3.3 per 1000 person-years; adjusted HR, 1.79; 95% CI, 1.21-2.67). In a secondary analysis, GLP-1 analogues were also associated with an increased risk of cholecystectomy (adjusted HR, 2.08; 95% CI, 1.08-4.02).CONCLUSIONS AND RELEVANCE The use of GLP-1 analogues was associated with an increased risk of bile duct and gallbladder disease. Physicians should be aware of this potential adverse event when prescribing these drugs.