Comparative effectiveness of GLP-1 receptor agonists on cardiovascular outcomes among adults with type 2 diabetes and moderate cardiovascular risk: emulation of a target trial

IF 7.4 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-09-20 DOI:10.1016/j.diabres.2025.112910

Stacey M. Sklepinski , Yihong Deng , Kavya Sindu Swarna , Jeph Herrin , Eric C. Polley , Joshua J. Neumiller , Rodolfo J. Galindo , Guillermo E. Umpierrez , Joseph S. Ross , Bijan J. Borah , Bradley A. Maron , Mindy M. Mickelson , Rozalina G. McCoy

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Abstract

Aim

To compare the cardiovascular outcomes of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among adults with type 2 diabetes mellitus (T2D) at moderate cardiovascular risk.

Methods

We emulated a target trial using claims data of adults with T2D at moderate cardiovascular risk who initiated dulaglutide, exenatide, liraglutide, or semaglutide between 01/01/2014–12/31/2021. Random treatment assignment was emulated by propensity scores and incorporated into inverse probability of treatment weighted (IPTW) Cox models. Outcomes were time to composite major adverse cardiovascular events (MACE: myocardial infarction, stroke, and all-cause mortality), expanded MACE (MACE, hospitalization for heart failure, and revascularization) and its components, and severe hypoglycemia.

Results

After IPTW, 35,572 patients initiated dulaglutide, 4376 initiated exenatide, 8843 initiated liraglutide, and 33,063 initiated semaglutide. Compared to dulaglutide, semaglutide was associated with lower risk of MACE (HR 0.85, 95CI % 0.78–0.93), expanded MACE (HR 0.92, 95CI % 0.87–0.96), all-cause mortality (HR 0.81, 95CI % 0.71–0.92), stroke (HR 0.82, 95CI % 0.70–0.97), and revascularization (HR 0.93, 95CI % 0.88–0.99), while liraglutide was associated with lower risk of MACE (HR 0.84, 95CI % 0.72–0.97) and all-cause mortality (HR 0.79, 95CI % 0.64–0.99).

Conclusions

Among GLP-1RAs, semaglutide and liraglutide were associated with the greatest cardiovascular risk reduction in patients with T2D at moderate cardiovascular risk.

Abstract Image

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GLP-1受体激动剂对成人2型糖尿病和中度心血管风险患者心血管结局的比较有效性：一项目标试验的模拟

目的：比较胰高血糖素样肽-1受体激动剂（GLP-1RAs）在中度心血管风险的成人2型糖尿病（T2D）患者中的心血管结局。方法：我们模拟了一项目标试验，使用了2014年1月1日至2021年12月31日期间服用杜拉鲁肽、艾塞那肽、利拉鲁肽或西马鲁肽的中度心血管风险的成人T2D患者的索赔数据。随机处理分配由倾向得分模拟，并纳入处理加权逆概率（IPTW） Cox模型。结果是复合主要不良心血管事件（MACE：心肌梗死、卒中和全因死亡）的时间，扩大的MACE （MACE，因心力衰竭住院和血运重建术）及其组成部分，以及严重低血糖。结果：IPTW后，35,572例患者开始使用杜拉鲁肽，4376例使用艾塞那肽，8843例使用利拉鲁肽，33,063例使用西马鲁肽。与dulaglutide相比，semaglutide与MACE （HR 0.85, 95CI% 0.78-0.93）、MACE扩大（HR 0.92, 95CI% 0.87-0.96）、全因死亡率（HR 0.81, 95CI% 0.71-0.92）、卒中（HR 0.82, 95CI% 0.70-0.97）和血运重建（HR 0.93, 95CI% 0.88-0.99）的风险较低相关，而利拉鲁肽与MACE （HR 0.84, 95CI% 0.72-0.97）和全因死亡率（HR 0.79, 95CI% 0.64-0.99）的风险较低相关。结论：在GLP-1RAs中，西马鲁肽和利拉鲁肽与中度心血管风险的T2D患者心血管风险降低相关最大。

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.