研究用于治疗2型糖尿病患者高血糖的肠促胰岛素类疗法相关的抑郁或自我伤害风险：一项使用英国临床实践研究数据链的队列研究。
Examining the risk of depression or self-harm associated with incretin-based therapies used to manage hyperglycaemia in patients with type 2 diabetes: a cohort study using the UK Clinical Practice Research Datalink.
作者信息
Gamble John-Michael, Chibrikov Eugene, Midodzi William K, Twells Laurie K, Majumdar Sumit R
机构信息
School of Pharmacy, Faculty of Science, University of Waterloo, Waterloo, Ontario, Canada.
School of Pharmacy, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
出版信息
BMJ Open. 2018 Oct 8;8(10):e023830. doi: 10.1136/bmjopen-2018-023830.
OBJECTIVES
To compare population-based incidence rates of new-onset depression or self-harm in patients initiating incretin-based therapies with that of sulfonylureas (SU) and other glucose-lowering agents.
DESIGN
Population-based cohort study.
SETTING
Patients attending primary care practices registered with the UK-based Clinical Practice Research Datalink (CPRD).
PARTICIPANTS
Using the UK-based CPRD, we identified two incretin-based therapies cohorts: (1) dipeptidyl peptidase-4 inhibitor (DPP-4i)-cohort, consisting of new users of DPP-4i and SU and (2) glucagon-like peptide-1 receptor agonists (GLP-1RA)-cohort, consisting of new users of GLP-1RA and SU, between January 2007 and January 2016. Patients with a prior history of depression, self-harm and other serious psychiatric conditions were excluded.
MAIN OUTCOME MEASURES
The primary study outcome comprised a composite of new-onset depression or self-harm. Unadjusted and adjusted Cox proportional hazards regression was used to quantify the association between incretin-based therapies and depression or self-harm. Deciles of High-Dimensional Propensity Scores and concurrent number of glucose-lowering agents were used to adjust for potential confounding.
RESULTS
We identified new users of 6206 DPP-4i and 22 128 SU in the DPP-4i-cohort, and 501 GLP-1RA and 16 409 SU new users in the GLP-1RA-cohort. The incidence of depression or self-harm was 8.2 vs 11.7 events/1000 person-years in the DPP-4i-cohort and 18.2 vs 13.6 events/1000 person-years in the GLP-1RA-cohort for incretin-based therapies versus SU, respectively. Incretin-based therapies were not associated with an increased or decreased incidence of depression or self-harm compared with SU (DPP-4i-cohort: unadjusted HR 0.70, 95% CI 0.51 to 0.96; adjusted HR 0.80, 95% CI 0.57 to 1.13; GLP-1RA-cohort: unadjusted HR 1.36, 95% CI 0.72 to 2.58; adjusted HR 1.25, 95% CI 0.63 to 2.50). Consistent results were observed for other glucose-lowering comparators including insulin and thiazolidinediones.
CONCLUSIONS
Our findings suggest that the two incretin-based therapies are not associated with an increased or decreased risk of depression or self-harm.
目的
比较起始使用基于肠促胰岛素的疗法的患者中，新发抑郁症或自我伤害的人群发病率与使用磺脲类药物（SU）及其他降糖药物的患者的发病率。
设计
基于人群的队列研究。
背景
在英国临床实践研究数据链（CPRD）注册的基层医疗诊所就诊的患者。
参与者
利用英国的CPRD，我们确定了两个基于肠促胰岛素的疗法队列：（1）二肽基肽酶-4抑制剂（DPP-4i）队列，由DPP-4i和SU的新使用者组成；（2）胰高血糖素样肽-1受体激动剂（GLP-1RA）队列，由GLP-1RA和SU的新使用者组成，时间跨度为2007年1月至2016年1月。排除有抑郁症、自我伤害及其他严重精神疾病既往史的患者。
主要观察指标
主要研究结局包括新发抑郁症或自我伤害的综合情况。采用未调整和调整后的Cox比例风险回归来量化基于肠促胰岛素的疗法与抑郁症或自我伤害之间的关联。使用高维倾向评分十分位数和降糖药物的同时使用数量来调整潜在的混杂因素。
结果
在DPP-4i队列中，我们确定了6206名DPP-4i新使用者和22128名SU新使用者；在GLP-1RA队列中，确定了501名GLP-1RA新使用者和16409名SU新使用者。对于基于肠促胰岛素的疗法与SU，DPP-4i队列中抑郁症或自我伤害的发病率分别为8.2例/1000人年和11.7例/1000人年，GLP-1RA队列中分别为18.2例/1000人年和13.6例/1000人年。与SU相比，基于肠促胰岛素的疗法与抑郁症或自我伤害的发病率增加或降低均无关联（DPP-4i队列：未调整的风险比[HR]为0.70，95%置信区间[CI]为0.51至0.96；调整后的HR为0.80，95%CI为0.57至1.13；GLP-1RA队列：未调整的HR为1.36，95%CI为0.72至2.58；调整后的HR为1.25，95%CI为0.63至2.50）。对于其他降糖对照药物，包括胰岛素和噻唑烷二酮类药物，也观察到了一致的结果。
结论
我们的研究结果表明，两种基于肠促胰岛素的疗法与抑郁症或自我伤害风险的增加或降低均无关联。
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