Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial
Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial
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DOI：
10.1016/s1474-4422(20)30173-3
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发表时间：
2020-07-01
期刊：
影响因子：
48
通讯作者：
Temelkova-Kurktschiev, Theodora
中科院分区：
文献类型：
--
作者：
Cukierman-Yaffe, Tali;Gerstein, Hertzel C.;Temelkova-Kurktschiev, Theodora
背景糖尿病是认知功能障碍的独立危险因素。我们的目的是探讨胰高血糖素样肽-1（GLP-1）受体激动剂dullavin和认知功能障碍之间的关联，作为探索性分析内的研究心血管事件与每周肠促胰岛素在糖尿病（REWIND）trial.Methods REWIND是一项随机，双盲安慰剂对照试验，在371个网站在24个国家。我们纳入了男性和女性（年龄≥ 50岁），患有确诊或新诊断的2型糖尿病和其他心血管危险因素，糖化血红蛋白高达9.5%（80 mmol/mol），最多服用两种口服降糖药物，伴或不伴基础胰岛素，体重指数至少为23 kg/m2。受试者被随机分配（1：1）每周一次皮下注射dulcantine（1.5 mg）或等体积的匹配安慰剂。使用计算机生成的代码进行随机化，并按研究中心分层。受试者和所有研究人员均对治疗分配设盲，直至数据库锁定。参与者至少每6个月随访一次卒中、心肌梗死或心血管或不明原因死亡的复合主要结局。在基线和随访期间使用蒙特利尔认知评估（莫卡）和数字符号替代测试（DSST）评估认知功能。我们在这里介绍了探索性的主要认知结果，这是第一次发生的随访评分的莫卡或DSST是1.5 SD或以上低于基线平均得分在参与者的国家。所有分析均采用意向治疗方法进行。REWIND试验注册于ClinicalTrials.gov，NCT 01394952。结果在2011年8月18日至2013年8月14日期间，9901名参与者被随机分配到dullavin（n=4949）或安慰剂（n=4952）组。在5.4年（IQR 5.1-5.9）的中位随访期间，8828名参与者提供了基线和一个或多个随访莫卡或DSST评分，其中4456名被分配为dullidine，4372名被分配为安慰剂。认知结局发生率为4.05/100患者-年，分配给dullipid的参与者和4.35/100患者-年，分配给安慰剂的人（风险比[HR] 0.93，95%CI 0.85-1.02; p=0.11）。在对个体标准化基线评分进行事后调整后，在那些被分配为dullavin的患者中，实质性认知障碍的风险降低了14%（HR 0.86，95%CI 0.79-0.95; p=0.0018）。明确指出了对这种药物的进一步研究，重点是大脑健康和认知功能。
Background Diabetes is an independent risk factor for cognitive impairment. We aimed to investigate the association between the glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide and cognitive impairment as an exploratory analysis within the Researching Cardiovascular Events With a Weekly Incretin in Diabetes (REWIND) trial.Methods REWIND is a randomised, double-blind placebo-controlled trial at 371 sites in 24 countries. We included men and women (aged >= 50 years) with either established or newly diagnosed type 2 diabetes and additional cardiovascular risk factors, glycated haemoglobin of up to 9.5% (80 mmol/mol) on a maximum of two oral glucose-lowering drugs with or without basal insulin, and a body-mass index of at least 23 kg/m(2). Participants were randomly assigned (1:1) subcutaneous injections once a week of either dulaglutide (1.5 mg) or an equal volume of matching placebo. Randomisation was done using a computer-generated code with stratification by site. Participants and all study personnel were masked to treatment allocation until the database was locked. Participants were followed up at least every 6 months for the composite primary outcome of stroke, myocardial infarction, or death from cardiovascular or unknown causes. Cognitive function was assessed at baseline and during follow-up using the Montreal Cognitive Assessment (MoCA) and Digit Symbol Substitution Test (DSST). We present here the exploratory primary cognitive outcome, which was the first occurrence of a follow-up score on MoCA or DSST that was 1.5 S Ds or more below the baseline mean score in the participant's country. All analyses were done using an intention-to-treat approach. The REWIND trial is registered with ClinicalTrials.gov, NCT01394952.Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were randomly assigned to either dulaglutide (n=4949) or placebo (n=4952). During median follow-up of 5.4 (IQR 5.1-5.9) years, 8828 participants provided a baseline and one or more follow-up MoCA or DSST scores, of whom 4456 were assigned dulaglutide and 4372 were assigned placebo. The cognitive outcome occurred in 4.05 per 100 patient-years in participants assigned dulaglutide and 4.35 per 100 patient-years in people assigned placebo (hazard ratio [HR] 0.93, 95% CI 0.85-1.02; p=0.11). After post-hoc adjustment for individual standardised baseline scores, the hazard of substantive cognitive impairment was reduced by 14% in those assigned dulaglutide (HR 0.86, 95% CI 0.79-0.95; p=0.0018).Interpretation Long-term treatment with dulaglutide might reduce cognitive impairment in people with type 2 diabetes. Further studies of this drug focused on brain health and cognitive function are clearly indicated.