Laboratory of Biostatistics, Epidemiology, and Public Health (Equipe d'Acceuil 2415), Faculty of Medicine, University of Montpellier, Montpellier, France2Department of Medical Pharmacology and Toxicology, Montpellier University Hospital, Montpellier, France.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada4Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada.
JAMA Intern Med. 2016 Oct 1;176(10):1474-1481. doi: 10.1001/jamainternmed.2016.1531.
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.
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.
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.
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.
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).
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.
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有关。迄今为止，尚无观察性研究评估这种可能的关联。
确定 DPP-4 抑制剂和 GLP-1 类似物的使用是否与 2 型糖尿病患者的胆管和胆囊疾病的发生率增加有关。
设计、地点和参与者：一项基于人群的队列研究将英国临床实践研究数据链接与医院发病统计数据库相链接，得出了一个 71369 名年龄在 18 岁或以上的患者队列，他们在 2007 年 1 月 1 日至 2014 年 3 月 31 日期间开始使用一种抗糖尿病药物（包括口服和注射药物）。
与目前至少使用 2 种口服抗糖尿病药物相比，目前使用 DPP-4 抑制剂和 GLP-1 类似物（单独或联合治疗）。
使用时间依赖性 Cox 比例风险模型来估计风险比（HRs）和 95%置信区间（CI），以评估因住院而导致的胆管和胆囊事件（胆石症、胆囊炎、胆管炎）的发生率，将目前使用 DPP-4 抑制剂和 GLP-1 类似物与目前使用至少 2 种口服抗糖尿病药物进行比较。
在 227994 人年的随访期间，71369 名患者中有 853 名因胆管和胆囊疾病住院（每 1000 人年发病率为 3.7；95%CI，3.5-4.0）。与目前至少使用 2 种口服抗糖尿病药物相比，目前使用 DPP-4 抑制剂与胆管和胆囊疾病的风险增加无关（每 1000 人年 3.6 比 3.3；调整后的 HR，0.99；95%CI，0.75-1.32）。相比之下，与目前至少使用 2 种口服抗糖尿病药物相比，GLP-1 类似物的使用与胆管和胆囊疾病的风险增加有关（每 1000 人年 6.1 比 3.3；调整后的 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的风险增加有关（调整后的 HR，2.08；95%CI，1.08-4.02）。
GLP-1 类似物的使用与胆管和胆囊疾病的风险增加有关。医生在开这些药物时应注意到这种潜在的不良事件。
