Wvan der Zanden Rogier, de Vries Frank, Lalmohamed Arief, Driessen Johanna H M, de Boer Anthonius, Rohde Gernot, Neef Cees, den Heijer Casper
Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands.
Department of Clinical Pharmacy and Toxicology, Maastricht University, Medical Centre+, Maastricht, Netherlands; Care and Public Health Research Institute (CAPHRI), Maastricht, Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht, The Netherlands; Department of Clinical Pharmacy, University Medical Centre Utrecht, Utrecht, The Netherlands.
PLoS One. 2015 Oct 15;10(10):e0139367. doi: 10.1371/journal.pone.0139367. eCollection 2015.
Dipeptidyl-peptidase-4 inhibitors (DPP4Is) are drugs for the treatment of type 2 diabetes mellitus (T2DM). There is increasing evidence that DPP4Is may result in suppression of the immune system and may increase the risk of infections such as pneumonia. Aim of this study was to evaluate the association between the use of DPP4Is and the risk of pneumonia in a population-based study.
We conducted a population-based cohort study using data from the world's largest primary care database, the UK Clinical Practice Research Datalink (CPRD). We selected all users of non-insulin antidiabetic drugs (NIADs), including DPP4Is, between 2007 and 2012. To each NIAD user, we matched randomly selected non-users. The NIAD user's first prescription defined the index date, which was then assigned to the matched non-users. Patients were followed from their first prescription until end of data collection or the first event of pneumonia, whichever came first. Cox regression analysis estimated the association between pneumonia and current use of DPP4Is versus 1) current use of other NIADs and 2) non-users. DPP4I use was then stratified to daily and cumulative dose. Analyses were statistically adjusted for age, sex, lifestyle factors and comorbidities and concomitant use of various other drugs.
Risk of pneumonia was not increased with current DPP4I use versus use of other NIADs, adjusted Hazard Ratio (HR) 0.70; 95% Confidence Interval (CI) 0.55-0.91. Also higher cumulative doses or daily doses did not further increase risk of pneumonia.
We found no increased risk of pneumonia in T2DM patients using DPP4Is compared to T2DM patients using other NIADs. Our finding is in line with direct and indirect evidence from observational studies and RCTs. There is probably no need to avoid prescribing of DPP4Is to elderly patients who are at risk of pneumonia.
二肽基肽酶-4抑制剂(DPP4Is)是用于治疗2型糖尿病(T2DM)的药物。越来越多的证据表明,DPP4Is可能会导致免疫系统受到抑制,并可能增加感染风险,如肺炎。本研究的目的是在一项基于人群的研究中评估使用DPP4Is与肺炎风险之间的关联。
我们使用来自世界上最大的初级保健数据库——英国临床实践研究数据链(CPRD)的数据进行了一项基于人群的队列研究。我们选取了2007年至2012年间所有使用非胰岛素抗糖尿病药物(NIADs)的患者,包括使用DPP4Is的患者。对于每一位使用NIADs的患者,我们随机匹配未使用者。使用NIADs患者的首张处方确定索引日期,然后将该日期分配给匹配的未使用者。患者从首张处方开始随访,直至数据收集结束或首次发生肺炎,以先发生者为准。Cox回归分析估计了肺炎与当前使用DPP4Is相比1)当前使用其他NIADs以及2)未使用者之间的关联。然后将DPP4I的使用情况按每日剂量和累积剂量进行分层。分析对年龄、性别、生活方式因素、合并症以及同时使用的各种其他药物进行了统计学调整。
与使用其他NIADs相比,当前使用DPP4Is并未增加肺炎风险,调整后的风险比(HR)为0.70;95%置信区间(CI)为0.55 - 0.91。更高的累积剂量或每日剂量也未进一步增加肺炎风险。
我们发现,与使用其他NIADs的2型糖尿病患者相比,使用DPP4Is的2型糖尿病患者发生肺炎的风险并未增加。我们的发现与观察性研究和随机对照试验的直接和间接证据一致。对于有肺炎风险的老年患者,可能无需避免开具DPP4Is处方。