近日，美国杜克大学医学中心David D’Alessio团队研究了替西帕肽与杜拉鲁肽治疗2型糖尿病的心血管结局。2025年12月18日，《新英格兰医学杂志》发表了这一成果。

替西帕肽是胰高血糖素样肽-1和葡萄糖依赖性胰岛素多肽受体的双重肠促胰岛素激动剂，对血糖控制和体重有良好的作用。对心血管预后的影响尚不确定。

研究组进行了一项主动对照、双盲、非劣效性试验，在该试验中，2型糖尿病和动脉粥样硬化性心血管疾病患者按1:1的比例随机分配，接受每周皮下注射替西帕肽（高达15mg）或杜拉鲁肽（1.5 mg），一种已被证明可降低心血管事件发生率的药物。主要终点是心血管原因、心肌梗死或中风的复合死亡，并对替西帕肽对杜拉鲁肽的非劣效性进行了检验，风险比的95.3%置信区间上限为1.05。小于1.00的上限被认为表明替西帕肽优于杜拉鲁肽。

随机分组共13299例患者；134例随后因不符合纳入标准而被排除。因此，修改意向治疗人群包括替西帕肽组6586例患者和杜拉鲁肽组6579例患者。患者平均（±SD）年龄为64.1±8.8岁，女性29.0%，平均体重指数（体重公斤除以身高米的平方）为32.6±5.5，平均糖化血红蛋白水平为8.4±0.9%，平均糖尿病病程为14.7±8.8年。替西帕肽组801例（12.2%）患者发生了主要终点事件，杜拉鲁肽组862例（13.1%）患者发生了主要终点事件（风险比为0.92；95.3%可信区间为0.83 ~ 1.01；非劣效性P=0.003；优效性P=0.09）。两组不良事件的发生率似乎相似，尽管在替西帕肽组观察到更多的胃肠道不良事件。

研究结果表明，在2型糖尿病和动脉粥样硬化性心血管疾病患者中，替西帕肽在心血管原因、心肌梗死或中风的复合死亡方面不逊于杜拉鲁肽。

附：英文原文

Title: Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes

Author: Stephen J. Nicholls, Imre Pavo, Deepak L. Bhatt, John B. Buse, Stefano Del Prato, Steven E. Kahn, A. Michael Lincoff, Darren K. McGuire, Debra Miller, Michael A. Nauck, Hiroshi Nishiyama, Steven E. Nissen, Naveed Sattar, Govinda Weerakkody, Russell J. Wiese, Bernard Zinman, Sophia Zoungas, Jan Basile, Melanie J. Davies, Francesco Giorgino, Monika Kellerer, Linong Ji, Tamas Varkonyi, Venu Menon, Jonathan C. Broder, Alan Herschtal, David D’Alessio

Issue&Volume: 2025-12-18

Abstract:

Background

Tirzepatide, a dual incretin agonist of the glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide receptors, has favorable effects on glycemic control and body weight. The effects on cardiovascular outcomes are uncertain.

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 incidence of cardiovascular events. 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 interval for the hazard ratio. An upper limit of less than 1.00 was considered to indicate superiority of tirzepatide to dulaglutide.

Results

A total of 13,299 patients underwent randomization; 134 were subsequently excluded because they did not meet inclusion criteria. The modified intention-to-treat population thus included 6586 patients in the tirzepatide group and 6579 in the dulaglutide group. 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. 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). The incidence of adverse events appeared to be similar in the two groups, although more gastrointestinal adverse events were observed in the tirzepatide group.

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.

DOI: NJ202512183932407

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2505928