Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes.

The effects on cardiovascular outcomes are uncertain.

其对心血管结果的影响尚不确定。

Methods

We conducted an active-comparator-controlled, double-blind, noninferiority trial in which patients with type 2 diabetes and atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to receive a weekly subcutaneous injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg), an agent that has been shown to reduce the incidenceof cardiovascular events.

我们开展了一项活性对照、双盲、非劣效试验，将2型糖尿病和动脉粥样硬化性心血管疾病的患者以1:1的比例随机分配，接受每周一次的皮下注射tirzepatide（最高剂量15 mg）或已显示出能减少心血管事件发生率的dulaglutide（1.5 mg）治疗。

The primary end point was a composite of death from cardiovascular causes, myocardial infarction, or stroke and was tested for noninferiority of tirzepatide to dulaglutide with a margin of 1.05 for the upper limit of the 95.3% confidence intervalfor the hazard ratio.

主要终点是心血管原因死亡、心肌梗死或中风的复合终点，通过设定危险比的95.3%置信区间的上限为1.05，测试tirzepatide对dulaglutide的非劣效性。

An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide.

认为上限小于1.00表明tirzepatide优于dulaglutide。

Results

A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria.

共有13,299名患者进行了随机分组；由于不符合纳入标准，随后排除了134名患者。

The modified intention-to-treatpopulation thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group.

因此，改良意向治疗人群包括6586名接受tirzepatide治疗的患者和6579名接受dulaglutide治疗的患者。

The mean (±SD) age of the patients was 64.1±8.8 years, 29.0% were women, the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 32.6±5.5, the mean glycated hemoglobin level was 8.4±0.9%, and the mean duration of diabetes was 14.7±8.8 years.

患者的平均（±标准差）年龄为64.1±8.8岁，29.0%为女性，平均体重指数（体重以千克为单位除以身高以米为单位的平方）为32.6±5.5，平均糖化血红蛋白水平为8.4±0.9%，糖尿病平均患病时间为14.7±8.8年。

A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority).

在tirzepatide组有801名患者（12.2%）和dulaglutide组有862名患者（13.1%）发生了主要终点事件（风险比，0.92；95.3%置信区间，0.83至1.01；P=0.003显示非劣效性；P=0.09显示优越性）。

The incidenceof adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group.

两组的不良事件发生率似乎相似，尽管在tirzepatide组观察到更多的胃肠道不良事件。

Conclusions

Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was noninferior to dulaglutide with respect to a composite of death from cardiovascular causes, myocardial infarction, or stroke.

在2型糖尿病和动脉粥样硬化性心血管疾病的患者中，tirzepatide在心血管原因死亡、心肌梗死或中风的复合终点方面与dulaglutide相比具有非劣效性。

(Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.).

(由礼来公司资助；SURPASS-CVOT临床试验注册号，NCT04255433。)