Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton, ON, Canada.
University of Edinburgh, Edinburgh, UK.
Lancet. 2019 Jul 13;394(10193):121-130. doi: 10.1016/S0140-6736(19)31149-3. Epub 2019 Jun 9.
BACKGROUND: Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A (HbA) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. METHODS: This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. FINDINGS: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA 7·2% [IQR 6·6-8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001). INTERPRETATION: Dulaglutide could be considered for the management of glycaemic control in middle-aged and older people with type 2 diabetes with either previous cardiovascular disease or cardiovascular risk factors. FUNDING: Eli Lilly and Company.
背景：三种不同的胰高血糖素样肽-1（GLP-1）受体激动剂可降低高心血管风险和高糖化血红蛋白 A（HbA）浓度的 2 型糖尿病患者的心血管结局。我们评估了 GLP-1 受体激动剂度拉糖肽在 2 型糖尿病患者的现有抗高血糖治疗方案基础上添加治疗时对主要不良心血管事件的影响，这些患者既往有心血管疾病或心血管风险因素，且血糖控制范围广泛。
方法：这是一项在 24 个国家的 371 个地点进行的多中心、随机、双盲、安慰剂对照试验。年龄至少 50 岁的男性和女性，患有 2 型糖尿病，且既往有心血管事件或心血管危险因素，按 1:1 比例随机分配接受每周皮下注射度拉糖肽（1.5 mg）或安慰剂。随机分配由计算机生成的随机代码，并按地点分层。所有研究者和参与者对治疗分配均不知情。参与者每 6 个月至少随访一次，以评估心血管和其他严重临床结局的发生情况。主要复合终点为非致死性心肌梗死、非致死性卒中和心血管原因（包括原因不明）所致死亡的首次发生，该终点在意向治疗人群中进行评估。这项研究在 ClinicalTrials.gov 注册，编号为 NCT01394952。
发现：在 2011 年 8 月 18 日至 2013 年 8 月 14 日期间，9901 名参与者（平均年龄 66.2 岁[标准差 6.5]，中位糖化血红蛋白 7.2%[四分位距 6.6-8.1]，4589[46.3%]为女性）被纳入并随机分配接受度拉糖肽（n=4949）或安慰剂（n=4952）。在中位随访 5.4 年（四分位距 5.1-5.9）期间，主要复合结局在度拉糖肽组中发生率为 12.0%（594 例患者），发病率为每 100 人年 2.4 例，安慰剂组发生率为 13.4%（663 例患者），发病率为每 100 人年 2.7 例（风险比[HR]0.88，95%置信区间 0.79-0.99；p=0.026）。两组全因死亡率无差异（度拉糖肽组 536 例[10.8%]，安慰剂组 592 例[12.0%]；HR 0.90，95%置信区间 0.80-1.01；p=0.067）。在随访期间，与接受安慰剂的参与者（1687 例，34.1%）相比，接受度拉糖肽的参与者（2347 例，47.4%）报告胃肠道不良事件的更多（p<0.0001）。
结论：对于既往有心血管疾病或心血管危险因素的 2 型糖尿病中年龄较大的中年人和老年人，度拉糖肽可考虑用于血糖控制。
注：该译文是基于 ChatGPT 生成的草稿，可能存在一些不准确或不流畅的地方，仅供参考。
Lancet Diabetes Endocrinol. 2020-1-7
Pharmaceutics. 2025-8-9
Int J Mol Sci. 2025-8-21
Nat Rev Endocrinol. 2025-8-22
Zotero 插件