Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht, the Netherlands.
Diabetes Care. 2011 Feb;34(2):369-74. doi: 10.2337/dc10-1771.
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. They inactivate incretin hormones but also have many other effects throughout the body, among which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections.
A nested case-control was conducted using VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system. All other ADRs were considered controls. Reporting odds ratios (RORs) were calculated to estimate the strength of the association between different classes of antidiabetic drugs and the reporting of infections.
We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of infections was higher for patients using DPP-4 inhibitors compared with users of biguanides (ROR 2.3 [95% CI 1.9-2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI 8.6-17.5]) was significantly associated with use of DPP-4 inhibitors.
This study indicates an increased reporting of infections, in particular upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underreporting, the Weber-effect, reporting bias) should be taken into account. Therefore, further research is needed to evaluate this suspicion and the underlying mechanism.
二肽基肽酶-4（DPP-4）抑制剂是一类新型的抗糖尿病药物。它们能使肠降血糖素失活，但也会对全身产生许多其他影响，其中包括对免疫系统的影响。这可能会导致感染风险增加。本研究评估了使用 DPP-4 抑制剂与感染报告之间的关联。
使用世界卫生组织-药物不良反应（WHO-ADR）数据库 VigiBase 进行嵌套病例对照研究。基础队列由抗糖尿病药物的药物不良反应（ATC 代码 A10）组成。根据监管活动医学词典（MedDRA）分类系统，病例定义为感染药物不良反应。所有其他药物不良反应均被视为对照。报告比值比（ROR）用于估计不同类别的抗糖尿病药物与感染报告之间的关联强度。
我们在 106469 例药物不良反应报告中确定了涉及 305415 例可疑抗糖尿病药物的药物不良反应，其中 8083 例涉及 DPP-4 抑制剂单药治疗。总体而言，与使用二甲双胍的患者相比，使用 DPP-4 抑制剂的患者感染报告更高（ROR 2.3 [95%CI 1.9-2.7]）。使用 DPP-4 抑制剂与上呼吸道感染（ROR 12.3 [95%CI 8.6-17.5]）的报告显著相关。
本研究表明，与其他抗糖尿病药物相比，使用 DPP-4 抑制剂的患者感染报告增加，特别是上呼吸道感染。然而，应考虑到自发报告系统的局限性（例如，漏报、韦伯效应、报告偏倚）。因此，需要进一步研究来评估这种怀疑和潜在机制。
