Cardiovascular Effects of Alogliptin, Linagliptin, Saxagliptin, and Sitagliptin: A Target Trial Emulation of a Comparative Effectiveness Study

IF 4.4 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Practice Pub Date : 2026-09-01 Epub Date: 2026-04-08 DOI:10.1016/j.eprac.2026.04.004

Urja N. Kalathiya BS, Kimberly Yuang MD, Jeph Herrin PhD, Kavya Sindhu Swarna MPH, Yihong Deng PhD, Eric C. Polley PhD, Joshua J. Neumiller PharmD, Rodolfo J. Galindo MD, Guillermo E. Umpierrez MD, Joseph S. Ross MD, MHS, Juan P. Brito MD, Victor M. Montori MD, Bijan J. Borah PhD, Bradley A. Maron MD, Mindy M. Mickelson MA, Rozalina G. McCoy MD, MS

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引用次数: 0

Abstract

Objective

To compare major adverse cardiovascular event (MACE) risks among available dipeptidyl peptidase-4 inhibitors among adults with type 2 diabetes at moderate cardiovascular risk.

Methods

Using claims data of enrollees in commercial, Medicare Advantage, and traditional Medicare plans between 2014 and 2021, we identified adults (≥21 years) with type 2 diabetes, moderate cardiovascular risk, and not requiring insulin who initiated alogliptin, linagliptin, saxagliptin, or sitagliptin. Random treatment assignment was emulated using propensity scores estimated using the super learner ensemble and incorporated as inverse probability of treatment weights into Cox models examining MACE (myocardial infarction, stroke, all-cause mortality), heart failure hospitalization (HHF), arterial revascularization, and hypoglycemia requiring emergency department/hospital use, with weighted median follow-up times calculated for each treatment arm.

Results

The weighted study cohort included 184,660 patients starting alogliptin (N= 2541), linagliptin (N= 42,433), saxagliptin (N= 15,649), and sitagliptin (N= 124,038) with median weighted follow-up of 39.5 (95% CI 35.8-41.6), 40.9 (95% CI 40.5-41.3), 42.6 (95% CI 41.7-43.3), and 42.4 (95% CI 42.2-42.6) months, respectively. One year after DDP4i initiation, MACE rates were 2.2%, 2.2%, 2.0%, and 1.7% for sitagliptin, linagliptin, saxagliptin, and alogliptin, respectively; HHF rates were 0.42%, 0.41%, 0.41%, and 0.37%; and hypoglycemia rates were 0.2%, 0.2%, 0.2%, and 0.2%. Saxagliptin was associated with modestly decreased risk of MACE vs sitagliptin (HR 0.94; 95% CI 0.88-0.99) and linagliptin (HR 0.94; 95% CI 0.87-1.00). There was no significant difference in HHF or hypoglycemia risk among the study drugs.

Conclusion

Risks of MACE, HHF, and hypoglycemia were comparable with all DPP4i. Choice of medication may be determined based on local availability.

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阿格列汀、利格列汀、沙格列汀和西格列汀对心血管的影响：一项比较有效性研究的目标试验模拟。

目的：比较中度心血管风险的成人2型糖尿病患者中可用的二肽基肽酶-4 （DPP4）抑制剂的主要不良心血管事件（MACE）风险。方法：使用2014-2021年间商业、医疗保险优势和传统医疗保险计划入组者的索赔数据，我们确定了患有2型糖尿病、中度心血管风险、不需要胰岛素的成年人（≥21岁），他们开始使用阿格列汀、利格列汀、沙格列汀或西格列汀。随机治疗分配使用使用超级学习者集合估计的倾向得分进行模拟，并将治疗权重的逆概率纳入检查MACE（心肌梗死、中风、全因死亡率）、心力衰竭住院（HHF）、动脉血运重建术和需要急诊科/医院使用的低血糖的Cox模型中，并计算每个治疗组的加权中位随访时间。结果：加权研究队列包括184,660例患者，阿格列汀（N=2,541）、利格列汀（N=42,433）、沙格列汀（N=15,649）和西格列汀（N=124,038）开始使用，中位加权随访时间分别为39.5 （95%CI 35.8-41.6）、40.9 （95%CI 40.5-41.3）、42.6 （95%CI 41.7-43.3）和42.4 （95%CI 42.2-42.6）个月。DDP4i启动1年后，西格列汀、利格列汀、沙格列汀和阿格列汀的MACE率分别为2.2%、2.2%、2%和1.7%；HHF发生率分别为0.42%、0.41%、0.41%和0.37%；低血糖率分别为0.2%,0.2%,0.2%,0.2%。沙格列汀与西格列汀（HR 0.94; 95%CI 0.88-0.99）和利格列汀（HR 0.94; 95%CI 0.87-1.00）相比，MACE风险适度降低。在研究药物中，HHF和低血糖的风险没有显著差异。结论：MACE、HHF和低血糖的风险与所有DPP4i具有可比性。药物的选择可以根据当地的可用性来决定。

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来源期刊

Endocrine Practice ENDOCRINOLOGY & METABOLISM-

CiteScore

7.60

自引率

2.40%

发文量

546

审稿时长

41 days

期刊介绍： Endocrine Practice (ISSN: 1530-891X), a peer-reviewed journal published twelve times a year, is the official journal of the American Association of Clinical Endocrinologists (AACE). The primary mission of Endocrine Practice is to enhance the health care of patients with endocrine diseases through continuing education of practicing endocrinologists.